Cancer Research and Treatment

Original Articles

Genetic Variant at 6p21.1 Impairs APOBEC2 in Hypoxic Mitophagy via HIF-1α/BNIP3 in Gastric Cancer: Zhonghua Zheng, Qian Li, Yuanliang Gu, Xinxiang Gao, Xinya Wang, Yan Zhang, Fangmei An, Qiang Zhan, Shuangshuang Yin, Yun Gao, Rui Peng, Li Liu, Erbao Zhang, Meng Zhu, Xiaofeng Chen, Gang Li, Hao Xu, Guangfu Jin, Caiwang Yan; Received October 30, 2025 Accepted May 8, 2026 Published online May 12, 2026; DOI: https://doi.org/10.4143/crt.2025.1194 [Accepted]

Abstract PDF: Purpose
Genome-wide association studies (GWASs) have identified single-nucleotide polymorphisms (SNPs) at the 6p21.1 locus associated with gastric cancer (GC) risk. However, the underlying biological mechanisms remain poorly understood.
Materials and Methods
We conducted fine-mapping analysis of the 6p21.1 region using large-scale GC GWAS data (10,254 cases and 10,914 controls). Functional annotation, luciferase reporter assays, Electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) experiments were performed to identify functional variants. The eQTL and colocalization analyses were used to determine the susceptibility gene. Mechanistic investigations included phenotypic assays under normoxic and hypoxic conditions, along with seahorse, immunofluorescence and ATP assays to assess mitochondrial function.
Results
We identified rs9381024 as the independent association signal at 6p21.1, with rs2235679, in strong linkage disequilibrium with rs9381024, emerging as a potential causative SNP. The T risk allele of rs2235679 reduced APOBEC2 expression by enhancing the binding of transcriptional repressor MZF1, thereby suppressing promoter activity. Expression analysis revealed a progressive decrease in APOBEC2 levels with gastric lesions severity, becoming nearly undetectable in GC tissues. Functionally, reduced APOBEC2 expression significantly promoted the proliferation of GC cells under hypoxic conditions but not under normoxia. Mechanistically, downregulation of APOBEC2 activated mitophagy to maintain mitochondria homeostasis via HIF-1α/BNIP3 pathway under hypoxia, ultimately driving tumor growth.
Conclusion
Our findings provide novel mechanistic insights into how genetic variants at 6p21.1 contribute to GC risk and progression, highlighting the tumor-suppressive role of APOBEC2.

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A Phase Ib/II Study of Pemigatinib in Combination with Paclitaxel in Patients with Gastric Cancer with FGFs/FGFRs Alterations: Minkyu Jung, Soo Hyun Park, Hyoyoung Kim, Youhyun Kim, Un-Jung Yun, Jiwoo Hwang, Hyo Song Kim, Choong-kun Lee, Hyunki Kim, Chung Lee, Dong-Hoe Koo, Hei-Cheul Jeung, Dae Young Zang, Eun-Kee Song, Sun Young Rha; Received December 10, 2025 Accepted May 1, 2026 Published online May 4, 2026; DOI: https://doi.org/10.4143/crt.2025.1352 [Accepted]

Abstract PDF: Purpose
Pemigatinib is a selective inhibitor of fibroblast growth factor receptors (FGFR) 1–3 with demonstrated activity in tumors harboring FGFR2 fusions or amplifications. This phase Ib/II trial assessed the efficacy and safety of pemigatinib in combination with paclitaxel in patients with recurrent or advanced gastric cancer exhibiting FGFs/FGFRs alterations.
Materials and Methods
Patients with gastric cancer harboring FGFs/FGFRs aberrations who experienced progression following first-line therapy were enrolled. The phase Ib component established the recommended phase II dose (RP2D); the phase II component evaluated clinical efficacy.
Results
Twelve patients were enrolled. The RP2D was determined as pemigatinib 13.5 mg/day (days 1–21) plus paclitaxel 80 mg/m² (days 1, 8, 15) every 4 weeks. Median progression-free and overall survival were 4.4 and 10.5 months, respectively. Patients with FGFR2 amplification (n=6) exhibited prolonged progression-free survival (6.5 vs. 3.5 months, p=0.049), while overall survival did not differ significantly. The objective response and disease control rates were 33.3% and 91.7%, respectively. The most frequent treatment-related adverse events were neutropenia (83.3%, grade ≥3: 58.3%) and hyperphosphatemia (83.3%, grade ≥3: 33.3%).
Conclusion
Pemigatinib plus paclitaxel demonstrated antitumor activity with an acceptable safety profile in FGFR2-amplified gastric cancer. Further investigation is warranted to elucidate resistance mechanisms and validate these findings in larger cohorts.

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Smoking, Alcohol, and Abdominal Obesity Increase Gastric Cancer Risk after Helicobacter pylori Eradication: Joo Hyun Lim, Cheol Min Shin, Kyungdo Han, Jin-Hyung Jung, Jinju Choi, Eun Hyo Jin, Seung Joo Kang, Dong Ho Lee; Received November 3, 2025 Accepted December 30, 2025 Published online January 2, 2026; DOI: https://doi.org/10.4143/crt.2025.1200 [Accepted]

Abstract PDF: Purpose
Helicobacter pylori is the single most important risk factor for gastric cancer (GC). However, H. pylori eradication (HPE) does not eliminate risk of GC. To clarify the association of lifestyle factors with GC risk after HPE.
Materials and Methods
Using the Korean National Health Insurance Services (NHIS) database, adult individuals who claimed HPE between 2010 and 2016 were analyzed. The adjusted hazard ratios (aHR) for GC were analyzed according to the lifestyle status including smoking (never; light [<10PY]; moderate [10-20PY]; heavy [≥20PY]), alcohol (none; mild [<30g/day]; heavy [30g/day]), and abdominal obesity by using Cox proportional hazard model.
Results
During a median follow-up period of 6.7 years, 9,754 individuals were newly diagnosed with GC among the total of 1,282,702 subjects. Compared with never smokers, moderate (aHR 1.12 [95%CI 1.04-1.20]) and heavy smokers (1.34 [1.27-1.42]) had greater risks of post-HPE GC with dose-response manner. Heavy drinkers had increased risk of GC (1.23 [1.15-1.32]) compared with non-drinkers, and those with abdominal obesity had slightly elevated GC risk compared with those without that (1.11 [1.06-1.15]). In subgroup analyses, those who had HPE at age ≥ 55 were shown to be more affected by the unhealthy lifestyles (smoking [p-for-interaction <0.01], alcohol [0.03], and abdominal obesity [0.03]). Also, male showed greater risk increase by smoking habit [p-for-interaction 0.02] than female.
Conclusion
Unhealthy lifestyles like smoking, alcohol, and abdominal obesity were shown as risk factors for post-HPE GC. Those with late HPE were more likely to be affected by unhealthy lifestyles.

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Zolbetuximab Plus Chemotherapy as First-Line Treatment in Patients with Claudin 18.2-Positive, HER2-Negative, Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma: Korean Population Subgroup—Combined Efficacy and Safety Analysis from SPOTLIGHT and GLOW: Keun-Wook Lee, Sang Cheul Oh, Jong Gwang Kim, Sun Jin Sym, Byoung Yong Shim, Seok Yun Kang, In-Ho Kim, Jwa Hoon Kim, Hong Jae Chon, Sang-Hee Cho, Eun-Kee Song, Do-Youn Oh, Jin-Soo Kim, Young Iee Park, Won Ki Kang, Hyung-Don Kim, Janise Lee, Miri Yi, Min-Hee Ryu; Received August 28, 2025 Accepted December 4, 2025 Published online December 5, 2025; DOI: https://doi.org/10.4143/crt.2025.935 [Accepted]

Abstract PDF: Purpose
The phase 3 SPOTLIGHT and GLOW trials, in patients with claudin 18 isoform 2–positive, human epidermal growth factor receptor 2–negative, locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma, demonstrated statistically significant and clinically meaningful improvement in progression-free survival (PFS) and overall survival (OS) with first-line zolbetuximab plus chemotherapy versus placebo plus chemotherapy. This analysis evaluated efficacy and safety in the Korean subgroup from SPOTLIGHT and GLOW.
Materials and Methods
Patients were randomized 1:1 to receive zolbetuximab plus chemotherapy or placebo plus chemotherapy (mFOLFOX6 [modified folinic acid, 5-fluorouracil, and oxaliplatin] or CAPOX [capecitabine and oxaliplatin]). Primary endpoint was PFS, assessed per RECIST v1.1 by independent review committee. Other efficacy and safety parameters were assessed.
Results
The Korean subgroup consisted of 49 patients in the zolbetuximab group and 47 in the placebo group. Median PFS (95% confidence interval [CI]) was 12.3 months (7.3-15.3), and median OS was 30.5 months (16.1-45.5) with zolbetuximab versus 8.1 months (4.2-10.4) and 15.8 months (11.8-19.7) with placebo, respectively. Most common TEAEs in patients who received zolbetuximab versus placebo were nausea (79.6% vs. 53.2%), vomiting (55.1% vs. 21.3%), and decreased appetite (53.1% vs. 23.4%). Treatment-related TEAEs led to discontinuation of zolbetuximab and placebo in 4.1% and 2.1% of patients, respectively.
Conclusion
Zolbetuximab plus chemotherapy demonstrated favorable PFS and OS versus placebo plus chemotherapy in the Korean subgroup, with numerically greater efficacy compared with the overall pooled population. This may be potentially attributable to low rates of zolbetuximab discontinuation and toxicity management.

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Association between FGFR2b Positivity and Survival Outcomes of Patients with Gastric Cancer Treated with First-Line Nivolumab Plus Chemotherapy: Hyung-Don Kim, Heonwoo Lee, Hyungeun Lee, Meesun Moon, Jaewon Hyung, Jungeun Ma, Young Soo Park, Min-Hee Ryu; Received June 6, 2025 Accepted November 22, 2025 Published online November 24, 2025; DOI: https://doi.org/10.4143/crt.2025.598 [Accepted]

Abstract PDF: Purpose
Fibroblast growth factor receptor 2b (FGFR2b) is a promising therapeutic target in gastric cancer; however, its clinical relevance in immune checkpoint inhibitor (ICI)-based chemotherapy remains unclear. Therefore, this study aims to evaluate the expression pattern and predictive value of FGFR2b in patients undergoing first-line nivolumab plus chemotherapy.
Materials and Methods
This single-center study included 503 patients diagnosed with gastric cancer. Among them, 296 underwent nivolumab-chemotherapy, while 207 underwent chemotherapy alone. FGFR2b expression was assessed via immunohistochemistry using samples collected after mid-2022. FGFR2b positivity was defined as membranous staining intensity of 2+/3+ in ≥ 1% of tumor cells, with ≥ 10% as overexpression, and 1–9% as low expression.
Results
FGFR2b overexpression and positivity were identified in 9.3% and 18.7% of cases, respectively. Discordance between paired biopsy and surgical samples was observed (20.0% and 40.0% for overexpression and positivity, respectively), indicating marked intratumoral heterogeneity. Among patients who underwent nivolumab-chemotherapy, FGFR2b overexpression and low expression were associated with favorable survival trends compared to those of FGFR2b-negative cases. These associations were not observed in patients treated with chemotherapy alone. Compared to chemotherapy alone, nivolumab-chemotherapy was associated with a greater survival benefit in patients with FGFR2b positivity. Multivariate interaction analyses revealed a significant interaction between FGFR2b expression and nivolumab-based chemotherapy.
Conclusion
FGFR2b expression exhibits substantial intratumoral heterogeneity in gastric cancer and may be linked to favorable outcomes in patients undergoing first-line ICI plus chemotherapy. Therefore, future studies should validate this finding, along with mechanistic investigations.

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Analysis of T-Cell Subsets Using Multiplex Immunohistochemistry and Clinical Outcomes of Immune Checkpoint Inhibitors in Advanced Gastric Cancer Patients: Tae-Yong Kim, Jeesun Yoon, Dae-Won Lee, Yoonjin Kwak, Hye Seung Lee, Do-Youn Oh; Received April 28, 2025 Accepted September 7, 2025 Published online September 9, 2025; DOI: https://doi.org/10.4143/crt.2025.458 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub: Purpose
As immunotherapy has become essential in the treatment of gastric cancer (GC), there has been growing interest in T-cells, which play a key role in immunotherapy. In this study, we evaluated the impact of T-cell subsets on immune responsiveness to immune checkpoint inhibitors (ICIs) in GC using multiplex immunohistochemistry (mIHC).
Materials and Methods
Eighty-four GC patients treated with ICIs were enrolled, and we repeated the staining-scanning-stripping procedure nine times to assess different kinds of T-cells or cell-surface immune checkpoints in a single tissue section.
Results
The proportions of patients with microsatellite instability (MSI)–high, Epstein-Barr virus (EBV), and non-MSI/non-EBV were 8.3%, 3.6%, and 88.1%. A high cytotoxic T-cell (T_cyto) density was related to longer overall survival (OS). GC with a high ratio of T_cyto/total T-cells (T_total) and a low ratio of regulatory T-cells (T_reg)/T_total showed better OS. A high density of programmed death-1 (PD-1)– or TIM-3–expressing T_cyto were also associated with longer OS than a low density of those. Among memory T-cells (T_mem) subsets, GC with a high ratio of memory T_cyto/T_mem and a low ratio of memory T_reg/T_mem showed prolonged OS. Better tumor responses were observed in GC with a high ratio of T_cyto/T_total and memory T_cyto/T_mem.
Conclusion
T-cell subsets within the tumor microenvironment were associated with the clinical efficacy of ICIs in GC. PD-1– or TIM-3–expressing T-cells were also associated with response to ICIs, while T_mem subsets were associated with survival. mIHC is a feasible method for evaluating T-cell subsets in archival gastric tumor tissue.

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Healthy Behaviors and All-Cause Mortality among Korean Gastric Cancer Survivors: Donghyun Won, Jeeyoo Lee, Sooyoung Cho, Ji Yoon Baek, Hyuk-Joon Lee, Aesun Shin; Received February 14, 2025 Accepted September 1, 2025 Published online September 3, 2025; DOI: https://doi.org/10.4143/crt.2025.177 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub: Purpose
The incidence, prevalence, and survival rates of gastric cancer are high, and the prognostic effects of healthy behaviors among survivors have not been well investigated. Therefore, we aimed to assess the effects of postdiagnosis healthy behaviors and behavior changes after gastric cancer diagnosis on all-cause mortality.
Materials and Methods
As a population-based retrospective cohort study, we used a cancer public library sample DB of gastric cancer patients between 2012 and 2019. Information from regular health check-up examinations was used to investigate their anthropometric measures, physical activities, alcohol consumption, and smoking status before and after cancer diagnosis. Hazard ratios (HRs) for all-cause deaths with 95% confidence intervals (CIs) were estimated via the Cox proportional hazards model.
Results
We analyzed 9,717 gastric cancer patients and 5,929 of those as a subgroup to assess the effects of behavior changes. Reduced mortality was shown among cancer patients who met the recommended criteria after the cancer diagnosis for physical activity (adjusted HR, 0.67 [95% CI, 0.49 to 0.93], mean frequencies of moderate to vigorous physical activity per week: ≥ 5 days vs. 0 days) and smoking cessation (0.77 [0.61 to 0.97], smoking status: never-smokers vs. current smokers). Participants who reported enhancement in behaviors had significantly lower mortality than the others who reported no or limited changes in physical activity (0.73 [0.55 to 0.96]) and smoking status (0.56 [0.38 to 0.83]).
Conclusion
The current study highlights the advantages of physical activity and smoking cessation in reducing mortality, and these benefits are even greater when patients improve their behavior after cancer diagnosis.

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Clinicopathological Factors Influencing PD-L1 Expression and the Effect of Immune Checkpoint Inhibitors on Survival Outcomes in Patients with Gastric Cancer Depending on Sex in a Tertiary Hospital in South Korea: Jeong hwan Lee, Nayoung Kim, Ji-Hyun Kim, Hyeon Jeong Oh, Yeejin Kim, Yonghoon Choi, Hyemin Jo, Ho-Kyoung Lee, Jinju Choi, Yu Kyung Jun, Hyuk Yoon, Cheol Min Shin, Young Soo Park, Dong Ho Lee, Hye Seung Lee, So Hyun Kang, Young Suk Park, Sang-Hoon Ahn, Yun-Suhk Suh, Do Joong Park, Hyung Ho Kim, Ji-Won Kim, Jin Won Kim, Keun-Wook Lee, Won Chang, Yoon Jin Lee, Kyoung Ho Lee, Young Hoon Kim, Soyeon Ahn; Received January 31, 2025 Accepted August 5, 2025 Published online August 13, 2025; DOI: https://doi.org/10.4143/crt.2025.126 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub

Purpose
Programmed cell death ligand-1 (PD-L1) negatively regulates T-cell activation, and exhibits sex-based differences in expression and immune responses. This study investigated sex-related differences in clinicopathological factors influencing PD-L1 expression and the effect of immune checkpoint inhibitors (ICIs) on survival in gastric cancer (GC) patients in South Korea.
Materials and Methods
We analyzed a prospective cohort of 468 GC patients who underwent PD-L1 immunohistochemistry. Age, tumor characteristics, molecular features, and survival outcomes were compared by sex. Multivariate analyses, including Cox proportional hazards modeling with an interaction term for sex, were performed.
Results
Among 468 patients, 280 (59.8%) were PD-L1 positive. In the overall cohort, PD-L1 positivity was significantly associated with Epstein-Barr virus (EBV) infection (odds ratio [OR], 7.46; p < 0.001), antral location of GC (OR, 1.84; p=0.027), and macrosatellite instability–high (MSI-H) (OR, 5.04; p=0.027). Diffuse-type histology was inversely associated (OR, 0.22; p=0.041). In males, EBV (OR, 36.27) and antral location (OR, 2.38) were significant. In females, only MSI-H was significant (OR, 11.63). ICI-containing therapy significantly improved survival in males (p=0.012) but not in females (p=0.415). Cox regression showed a survival benefit from ICIs (hazard ratio, 0.70; p=0.080), with a borderline-significant interaction by sex (p=0.073).
Conclusion
PD-L1 expression and therapeutic efficacy of ICIs differ by sex in GC. EBV infection and antral tumor location were independent factors in males, while MSI-H status was significant in females. These findings highlight the importance of sex-based immunobiology in tailoring GC treatment strategies.

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Prognostic implications of PD-L1 expression in gastric cancer: systematic review and meta-analysis of studies published between 2018 and 2025
Gulnaz Yessultanova, Zhanat Komekbay, Indira Karibayeva, Anar Tulyayeva, Nurgul Kereyeva, Aigul Zhumasheva, Lunara Ishimova
BMC Cancer.2026;[Epub] CrossRef

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Microbial Dynamics across Molecular Subtypes and Prognostic Significance of Lactobacillus in Gastric Cancer: Soo Kyung Nam, Juhyeong Park, Sujin Oh, Yoonjin Kwak, Cheol Min Shin, Kyoung Un Park, Nak-Jung Kwon, Seong-Ho Kong, Do Joong Park, Hyuk-Joon Lee, Han-Kwang Yang, Hye Seung Lee; Received April 25, 2025 Accepted July 16, 2025 Published online July 17, 2025; DOI: https://doi.org/10.4143/crt.2025.449 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub: Purpose
Recent studies have revealed a diverse gastric microbiota beyond Helicobacter pylori, suggesting a role in gastric cancer (GC). We aimed to investigate the composition and characteristics of the microbiota in GC and non-cancerous gastric mucosa (NC), with a particular focus on their relationship to molecular subtypes.
Materials and Methods
We conducted 16S rRNA sequencing and whole transcriptomic analysis on fresh-frozen GC and NC tissue samples from 192 GC patients, as well as saliva samples from 12 GC patients and 18 healthy individuals. Microsatellite instability (MSI), Epstein-Barr virus (EBV) in situ hybridization, and immunohistochemistry for p53 and E-cadherin were used to define molecular subtypes.
Results
GC tissues exhibited significantly higher diversity compared to matched NC tissues, with microbial profiles marked by decreased Helicobacter and increased Streptococcus, Prevotella, and Lactobacillus. Saliva samples predominantly contained oral bacteria and exhibited distinct microbial profiles from gastric tissues. In GC tissue, Helicobacter abundance was negatively correlated with key immune checkpoint genes (CTLA-4, PDCD1, CD274, and LAG3), whereas Prevotella, Streptococcus, and Fusobacterium were positively correlated. MSI-high and EBV-positive subtypes showed lower levels of Helicobacter but higher levels of Lactobacillus, Prevotella, and Streptococcus compared to the epithelial-mesenchymal transition–like subtype. Notably, within MSI-high GC, a subgroup characterized by Lactobacillus-enriched and otherwise microbiota-depleted profiles was significantly associated with poorer overall and disease-free survival.
Conclusion
These findings underscore distinct microbial patterns across GC molecular subtypes, suggesting potential biomarkers for GC diagnosis and treatment.

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Nivolumab Plus Chemotherapy Versus Placebo Plus Chemotherapy in Korean Patients with HER2-Negative, Untreated, Unresectable Advanced or Recurrent Gastric or Gastroesophageal Junction Cancer: Subgroup Analysis of a Randomized, Multicenter, Double-Blind Phase 3 Trial (ATTRACTION-4): Yoon-Koo Kang, Min-Hee Ryu, Do-Youn Oh, Sang Cheul Oh, Sun Young Rha, Keun-Wook Lee, Ik Joo Chung, Sung Yong Oh, Sun Jin Sym, Won Ki Kang, Jong Gwang Kim, Byoung Yong Shim, In-Ho Kim, Jin Young Kim, Eun-Kee Song, Hyo-Jin Lee, Seok Yun Kang, Dong-Hoe Koo, So Yeon Oh; Received September 13, 2024 Accepted July 1, 2025 Published online July 2, 2025; DOI: https://doi.org/10.4143/crt.2024.913 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub

Purpose
We report the safety and efficacy of nivolumab+chemotherapy for first-line treatment of advanced or recurrent gastric or gastroesophageal junction cancer in the Korean subpopulation of the ATTRACTION-4 clinical trial.
Materials and Methods
ATTRACTION-4 (NCT02746796) was a double-blind, randomized, placebo-controlled clinical trial of patients aged ≥ 20 years with histologically confirmed unresectable advanced or recurrent gastric or gastroesophageal junction cancer. Patients received nivolumab or placebo, both combined with physician-choice chemotherapy (oxaliplatin plus oral S-1 [tegafur–gimeracil–oteracil] [SOX] or oral capecitabine [CAPOX]).
Results
Overall, 464 patients were initially screened in Korea and 291 were randomized to nivolumab+chemotherapy (total/SOX/CAPOX: 148/66/82 patients) or placebo+chemotherapy (total/SOX/CAPOX: 143/61/82 patients). Centrally assessed progression-free survival (median, 14.75 vs. 8.34 months; hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.39 to 0.73; p < 0.001), overall survival (19.7 vs. 14.9 months; HR, 0.78; 95% CI, 0.60 to 1.02; p=0.065), overall response rate (54.7% vs. 47.6%), and duration of response (16.03 vs. 9.86 months) favored nivolumab+chemotherapy vs. placebo+chemotherapy. Grade ≥ 3 treatment-related adverse events (TRAEs) (56.1% vs. 44.1%), and any-grade endocrine (9.5% vs. 4.2%), hepatic (23.0% vs. 14.7%), hypersensitivity and infusion reactions (15.5% vs. 7.0%), renal (4.1% vs. 0.7%), and skin (44.6% vs. 23.1%) TRAEs tended to be more frequent in the nivolumab+chemotherapy group.
Conclusion
These findings demonstrate the clinical benefit of nivolumab combined with chemotherapy (either SOX or CAPOX) for first-line treatment of gastric cancer/gastroesophageal junction cancer in Korean patients.

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Claudin18.2 promote gastric cancer proliferation by activating MCM2/5
Bowen Zheng, Miao Fu, Fanzhuoran Lou, Yuting He, Lingying Zhao, Xintian Huang, Xiaowen Xie, Weijuan Tan, Quan Chen, Wenqing Zhang, Yongxiang Hong, Kaiyi Rong, Yuyan Lu, Ping Zhan, Jingke Tu, Huibo Shi, Tianhui Hu, Li Xiao
Scientific Reports.2026;[Epub] CrossRef
Skin toxicity induced by chemotherapy or molecular targeted therapy combined with immune checkpoint inhibitors in Asian patients: A literature review by the Japanese Pharmacist-led Oncodermatology Study Team
Yohei Iimura, Junichi Higuchi, Akimitsu Maeda, Kazuhiro Shimomura, Hirotoshi Iihara, Hironori Fujii, Takuya Iwamoto, Yoshitaka Saito, Hisanaga Nomura, Keiko Komori, Hidenori Tokuda, Ryuta Urakawa, Tatsuya Sumiya, Ryosuke Yanai, Mariko Kono, Masaki Ihira,
International Journal of Clinical Oncology.2026;[Epub] CrossRef
Overcoming diagnostic pitfalls in primary gastric squamous cell carcinoma: the imperative of adequate sampling in an elderly female patient, case report
Wanhui Dong, Li Cheng, Jing Xu, Sheng Xu, Yuling Yin, Qingming Sun, Yong Wu, Yuling Leng
Frontiers in Oncology.2025;[Epub] CrossRef

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Gastrointestinal cancer

Discrepancy between Genetically Predicted and Observed Alcohol Intake and Its Impact on Gastric Cancer Susceptibility: Ga-Eun Yie, Cheol Min Shin, Kyungtaek Park, Jinyeon Jo, Ah Ra Do, Sungkyoung Choi, Jung Hun Ohn, Sejoon Lee, Jeongseon Kim, Sun Ha Jee, Seung Joo Kang, Nayoung Kim, Sungho Won; Cancer Res Treat. 2026;58(2):563-572. Published online May 30, 2025; DOI: https://doi.org/10.4143/crt.2025.109

Abstract PDF Supplementary Material PubReader ePub: Purpose
We aimed to investigate how genetic predisposition to drinking and gastric cancer (GC) modifies the association between alcohol consumption and GC risk in the Korean population.
Materials and Methods
Polygenic risk scores for GC (PRS-GC) and alcohol consumption (PRS-Alcohol) were formulated using genome-wide association results from BioBank Japan. Validation was performed using Korean cohorts (SNUBH-GENIE cohort), incorporating 8,846 controls and 531 patients with GC. Subsequently, these PRSs were applied to an independent Korean cohort of 67,771 participants, including 313 patients with GC during the follow-up for 14 years (KoGES cohort).
Results
In KoGES cohort, the influence of alcohol consumption on GC risk was significantly altered by the PRS-GC and exhibited a synergistic interaction effect. PRS-Alcohol itself shows a negative correlation with GC risk. However, when actual alcohol consumption significantly exceeded genetically predicted levels, the risk of alcohol-related GC was notably increased (adjusted hazard ratio, 1.32; 95% confidence interval, 1.01 to 1.72). Heavy drinkers in the high–PRS-GC/low–PRS-Alcohol group had a 2.16 times higher risk of GC than non-to-light drinkers, which was prominent in males.
Conclusion
Korean drinkers with higher PRS-GC who consume alcohol more than genetically predicted levels are susceptible to GC. PRS-GC and PRS-Alcohol may be beneficial for assessing the impact of alcohol consumption on GC risk in Koreans.

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RASSF4 Suppresses Gastric Tumor Growth through Activation of Chk2-p53 Signaling Axis: Soon-Ki Park, Min-Ju Kang, Kyung-Phil Ko, Sung-Gil Chi; Cancer Res Treat. 2026;58(2):544-562. Published online April 18, 2025; DOI: https://doi.org/10.4143/crt.2025.135

Abstract PDF Supplementary Material PubReader ePub

Purpose
Ras association domain family 4 (RASSF4) is a putative tumor suppressor that is frequently inactivated in multiple human cancers. However, its candidacy as a suppressor in gastric tumorigenesis remains undefined. To understand the role for RASSF4 in gastric tumorigenesis, we investigated its expression status in cancer cell lines and tissues and regulatory role in tumor growth.
Materials and Methods
RASSF4 expression was analyzed in 13 cancer cell lines and 20 carcinoma tissues using polymerase chain reaction and immunoblot assays. RASSF4 effect on cell proliferation and apoptosis was examined by flow cytometry, colony formation, and [3H]thymidine incorporation assays and its regulation of p53 was determined using cycloheximide chase, promoter reporter, and immunoprecipitation assays. Mouse xenograft assay was performed to verify RASSF4 effect on tumor growth and therapeutic response.
Results
RASSF4 expression is epigenetically inactivated in eight of 13 (61.5%) cancer cell lines and 15 of 20 (75%) primary carcinomas. RASSF4 suppresses cell proliferation by inducing a G2/M cell cycle arrest and enhances apoptotic response to therapeutic drugs. RASSF4 is induced in response to genotoxic agents to facilitate stress-induced apoptosis in a highly p53-dependent fashion. Mechanistically, RASSF4 stabilizes p53 through Chk2 activation and its apoptotic function is profoundly impaired by depletion of either p53 or Chk2. RASSF4 attenuates xenograft tumor growth and enhances tumor response to 5-fluorouracil. Clinically, RASSF4 expression correlates strongly with the overall survival of gastric cancer patients.
Conclusion
RASSF4 suppresses gastric tumor growth through the activation of the Chk2-p53 axis, illuminating the mechanistic consequence of its inactivation in gastric tumorigenesis.

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The Dual Role of RASSF4 in Tumorigenesis: Mechanisms and Epigenetic Targeting Strategies
Rui Tian, Yixin Wu, Wenbin Yuan, Lingli Tian, Rui Zhang, Hao Lyu, Shuai Xiao, Dong Guo, Qi Zhang, Declan William Ali, Marek Michalak, Cefan Zhou, Jingfeng Tang, Xing-Zhen Chen
Biology.2025; 14(9): 1289. CrossRef

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Deciphering the Risk of Developing Lung Cancer after the Diagnosis of Gastric Cancer with Genetic Evidence: A European and East Asian Populations–Based Mendelian Randomization Analysis: Jiansheng Chen, Aiming Zeng, Yunzhe Yu, Sida Sun, Liqun Liao, Siwei Huang, Zhongshan Yang, Junfeng Zhou, Weijie Wu; Cancer Res Treat. 2026;58(1):242-251. Published online April 18, 2025; DOI: https://doi.org/10.4143/crt.2024.875

Abstract PDF Supplementary Material PubReader ePub: Purpose
Lung cancer is frequently observed as a second primary malignancy following gastric cancer, yet the genetic causality between them remains uncertain. This study aims to evaluate the causal relationship between gastric and lung cancers using Mendelian randomization (MR) analysis.
Materials and Methods
Single nucleotide polymorphisms associated with gastric and lung cancers were selected from genome-wide association study in East Asian and European populations as instrumental variables. The causal effects between gastric and lung cancers were evaluated using univariable and multivariable MR analysis, with the inverse variance weighted (IVW) method serving as the primary criterion. Heterogeneity and sensitivity analyses were performed to ensure the robustness of the findings.
Results
Univariable MR analysis demonstrated that genetic susceptibility to gastric cancer in the European population was significantly associated with an increased risk of lung cancer (IVW: odds ratio [OR], 1.285; 95% confidence interval [CI], 1.072 to 1.541; p=6.83E-03), which was consistently validated in the East Asian population (IVW: OR, 1.356; 95% CI, 1.114 to 1.651; p=2.40E-03). Multivariable MR analysis further indicated that the significant positive causal relationship between gastric cancer and lung cancer persisted in both populations after adjusting for confounding factors (all p < 0.05). Conversely, no significant causal relationship was observed for the risk of developing gastric cancer following the diagnosis of lung cancer in either population (p > 0.05).
Conclusion
This study confirms that genetic susceptibility to gastric cancer increases the risk of lung cancer. This finding provides a theoretical basis for exploring the underlying biological mechanisms and suggests that enhancing lung cancer screening in patients with gastric cancer may be necessary to improve patient prognosis.

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Survival Rates of Patients with Gastric Cancer According to Age and Sex: A Large-Scale Study Using Data from 14,739 Patients: Yonghoon Choi, Nayoung Kim, Ji Hyun Kim, Hyeong Ho Jo, Hyeon Jeong Oh, Hye Seung Lee, Yu Kyung Jun, Hyuk Yoon, Cheol Min Shin, Young Soo Park, Dong Ho Lee, So Hyun Kang, Young Suk Park, Sang-Hoon Ahn, Yun-Suhk Suh, Do Joong Park, Hyung Ho Kim, Ji-Won Kim, Jin Won Kim, Keun-Wook Lee, Won Chang, Yoon Jin Lee, Kyoung Ho Lee, Young Hoon Kim; Cancer Res Treat. 2026;58(1):252-263. Published online April 16, 2025; DOI: https://doi.org/10.4143/crt.2025.149

Abstract PDF Supplementary Material PubReader ePub

Purpose
The male predominance in the incidence of gastric cancer (GC) is established; however, sex differences in the prognosis of GC remain controversial. As such, this study analyzed the prognosis of patients with GC based on age and sex.
Materials and Methods
Data from 14,739 patients diagnosed with GC at Seoul National University Bundang Hospital between 2003 and 2023 were analyzed. Baseline characteristics, histological types of GC, overall and GC-specific survival rates (age and stage stratification), and associated risk factors were analyzed.
Results
Females were significantly younger (p < 0.001) and exhibited more gastric body cancers (p < 0.001) and tumors with diffuse-type or poorly differentiated histology (p < 0.001) than males. Females exhibited an advantage over males in terms of overall survival (p=0.004), but not in GC-specific survival. However, age stratification revealed significant sex differences, that females < 50 years of age exhibited survival disadvantages (p < 0.001); however, this trend was reversed with age, and females > 60 years exhibited survival advantages (p < 0.001) for both overall and GC-specific survival. This may be explained by the lower ratio of diffuse-type GC as females age. Furthermore, in the analysis according to stage, females with stage IV disease exhibited significant survival disadvantages, with significantly younger age and a higher proportion of diffuse-type GC which exhibits aggressive features, resulting in poorer survival than in males.
Conclusion
Age and stage stratification revealed significant differences in survival between the sexes, which can be helpful for public health strategies.

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Validation of Textbook Outcome in Gastric Surgery (TOGS) for Primary Gastric Cancer in an Eastern High-Volume Center
Ludovico Carbone, Yo-Seok Cho, Min Kyu Kang, Kyoyoung Park, Jane Chungyoon Kim, Sa-Hong Kim, Jeesun Kim, Nina Rebecca Kalaw, Yoonjin Kwak, Hye Seung Lee, Seong-Ho Kong, Do Joong Park, Daniele Marrelli, Han-Kwang Yang, Franco Roviello, Hyuk-Joon Lee
Annals of Surgical Oncology.2026;[Epub] CrossRef
Age-related prognostic trends in surgically resected female lymph node-metastatic gastric cancer: insights from SEER
Bozhi Hu, Yinli Zhang, Yingjiang Ye, Zhidong Gao, Chao Wang
International Journal of Clinical Oncology.2026;[Epub] CrossRef

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The Effect of Alcohol Consumption Behavior Changes on Gastric Cancer Risks Stratified by Sex in South Korea: Yonghoon Choi, Jieun Jang, Hyeong Ho Jo, Nayoung Kim; Cancer Res Treat. 2026;58(1):232-241. Published online April 1, 2025; DOI: https://doi.org/10.4143/crt.2024.591

Abstract PDF Supplementary Material PubReader ePub: Purpose
The effect of behavior changes in alcohol drinking on gastric cancer (GC) development, and the sex differences in those effects have not yet been fully elucidated. This study investigated the effect of behavior changes in alcohol drinking on the GC risk by sex.
Materials and Methods
The cohort consisted of 310,192 Koreans (≥ 40 years) from the National Health Insurance Service–Health Screening Cohort with a median follow-up period of 12 years. Subjects were classified according to alcohol consumption behavior changes (non-drinker, quitter, reducer, sustainer, and increaser). The independent effect of changes in alcohol drinking patterns or concurrent effect of alcohol on GC risk were evaluated using the Cox proportional hazard regression.
Results
In males, non-drinkers showed a lower risk of developing GC (hazard ratio [HR], 0.91; 95% confidence interval [CI], 0.84 to 0.98), whereas increasers showed a higher risk of GC than sustainers (HR, 1.11; 95% CI, 1.02 to 1.20). Starting to drink alcohol, even at a mild level, was associated with an increased GC risk, while a decreased GC risk was induced when alcohol consumption dose decreases to a mild from a moderate level among males. However, in females, only substantial change of alcohol consumption dose from non- to heavy-drinking was associated with increased GC risk (HR, 1.97; 95% CI, 0.98 to 3.96).
Conclusion
These results suggest that alcohol abstinence can reduce the risk of developing GC, particularly among males.

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Detection Ability of Quality of Life Changes and Responsiveness of the KOQUSS-40 and the EORTC QLQ-C30/STO22 in Patients Who Underwent Gastrectomy: A Prospective Comparative Study: Bang Wool Eom, Keun Won Ryu, Ji Yeong An, Yun-Suhk Suh, In Cho, Sung Geun Kim, Ji-Ho Park, Hoon Hur, Hyung-Ho Kim, Sang-Hoon Ahn, Sun-Hwi Hwang, Hong Man Yoon, Ki Bum Park, Hyoung-Il Kim, In-Gyu Kwon, Han-Kwang Yang, Byoung-Jo Suh, Sang-Ho Jeong, Tae-Han Kim, Oh Kyoung Kwon, Hye-Seong Ahn, Ji Yeon Park, Ki Young Yoon, Myoung Won Son, Seong-Ho Kong, Young-Gil Son, Geum Jong Song, Jong Hyuk Yun, Jung-Min Bae, Do Joong Park, Sol Lee, Jun-Young Yang, Kyung Won Seo, You-Jin Jang, So Hyun Kang, Joongyub Lee, Hyuk-Joon Lee, on behalf of KOrean QUality of life in Stomach cancer patients Study group (KOQUSS); Cancer Res Treat. 2026;58(1):221-231. Published online March 5, 2025; DOI: https://doi.org/10.4143/crt.2024.1104

Abstract PDF Supplementary Material PubReader ePub

Purpose
The aim of this study is to compare the detection ability of quality of life (QoL) changes and responsiveness of the KOrean QUality of life in Stomach cancer patients Study group (KOQUSS)-40 and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ).
Materials and Methods
A multicenter prospective observational study was conducted to evaluate QoL changes after various gastrectomies between January 2021 and April 2022. Participants were instructed to complete the KOQUSS-40 and EORTC QLQ-C30/STO22 preoperatively and at 1, 3, 6, and 12 months postoperatively. QoL changes over time and QoL responsiveness were assessed for each questionnaire.
Results
Data from 491 patients who underwent curative gastrectomy for gastric cancer at 22 institutions were analyzed. The summary scores of the KOQUSS-40 and EORTC QLQ-STO22 showed significant differences between the total and proximal gastrectomy groups (p=0.044 and p=0.038, respectively), but no difference was observed for the EORTC QLQ-C30. Dysphagia on the KOQUSS-40 was significantly different between the total and proximal gastrectomy groups (p=0.031); however, dysphagia on the EORTC QLQ-STO22 did not differ. The responsiveness of the KOQUSS-40 was similar to that of the EORTC QLQ in patients who experienced ≥ 10% body weight loss, but approximately 10% less in patients receiving adjuvant chemotherapy than the EORTC QLQ.
Conclusion
KOQUSS-40 has several advantages over EORTC QLQ-C30/STO22 when comparing QoL between the total and proximal gastrectomy groups. The findings provide information for researchers investigating the QoL of patients who have undergone curative gastrectomy for gastric cancer.

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Long-term quality of life, financial toxicity, and decision regret following therapeutic and prophylactic gastrectomy for cancer
Frank G. Lee, Jack W. Sample, Chun Fan, Robert A. Vierkant, Sara K. Daniel, Steven Bowers, Nabil Wasif, Mark J. Truty, Michael L. Kendrick, Cornelius A. Thiels, Travis E. Grotz
Gastric Cancer.2026; 29(3): 635. CrossRef
The efficacy of early progressive resistance exercise in the postoperative management of pancreaticoduodenectomy for pancreatic cancer: a randomized controlled trial
Xuexue Liu, Neng Shi, Rui Li, Yuan Song
Frontiers in Surgery.2025;[Epub] CrossRef
Improvement in Quality of Life After Early Interactive Human Coaching via a Mobile App in Postgastrectomy Patients With Gastric Cancer: Prospective Randomized Controlled Trial
Bang Wool Eom, Mira Han, Hong Man Yoon, Young-Woo Kim, So Young Kim, Jin Myoung Oh, Gyung Ah Wie, Keun Won Ryu
JMIR mHealth and uHealth.2025; 13: e75445. CrossRef

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General

Long-term Immunogenicity of the 13-valent Pneumococcal Conjugate Vaccine during Adjuvant Chemotherapy in Patients with Gastric and Colorectal Cancer: A 5-Year Follow-up of a Randomized Controlled Trial: Hyeon-Jong Kim, Hyunjin Bang, Hyun-Jung Shim, Jun Eul Hwang, Sang-Hee Cho, Ik-Joo Chung, Seung Ji Kang, Jong Gwang Kim, Seung-Hoon Beom, A-Yeung Jang, Joon Young Song, Woo Kyun Bae; Cancer Res Treat. 2026;58(1):61-70. Published online February 12, 2025; DOI: https://doi.org/10.4143/crt.2024.1083

Abstract PDF Supplementary Material PubReader ePub: Purpose
Current guidelines recommend vaccination at least 2 weeks before chemotherapy initiation to optimize the immune response despite limited evidence. Our previous study indicated no differences in short-term immune response for the 13-valent pneumococcal conjugate vaccine (PCV13) according to the vaccination timing. This study aims to investigate the long-term efficacy of PCV13 and clinical factors associated with the respective antibody response.
Materials and Methods
Patients with gastric or colorectal cancer who received adjuvant chemotherapy were enrolled and divided into two groups: vaccinated 2 weeks before chemotherapy (arm A) and vaccinated concurrently with chemotherapy (arm B). Serum samples were collected before vaccination and in one month, 3 years, and 5 years. Immune responses were measured using enzyme-linked immunosorbent assay and multiplex opsonophagocytosis assay.
Results
Including 63 patients, both groups showed an initial increase in the geometric mean titers of opsonophagocytic activity and the geometric mean concentrations of serotype-specific IgG levels after one month, followed by a decline at 3 and 5 years, particularly for serotypes 1, 14, 18C, and 19A. Despite the decline, global protection was maintained for 5 years, although global response decreased. The two arms did not show significant differences in immunogenicity nor in factors such as vaccination timing, age, cancer type, or chemotherapy regimen.
Conclusion
Vaccination timing is not a significant factor for the immunogenicity of PCV13 in cancer patients undergoing adjuvant chemotherapy. Global protection against pneumococcal infection was sustained for > 5 years, and global response remained in over half of patients.

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Review Article

The Current Evidence and Future Direction of Adjuvant Treatment for Gastric Cancer in the Era of Precision Medicine: Jong Hyuk Yun, Yoon Young Choi, Jae-Ho Cheong; Cancer Res Treat. 2025;57(3):621-634. Published online January 23, 2025; DOI: https://doi.org/10.4143/crt.2024.1222

Abstract PDF PubReader ePub

Although gastric cancer remains a significant global health burden, its treatment strategies vary across different geographical regions, leading to distinct guidelines. In Asia, particularly in Korea, D2 gastrectomy followed by adjuvant chemotherapy has been established as the standard treatment for stage II/III gastric cancer based on landmark clinical trials. However, this “one-size-fits-all” approach requires refinement as emerging evidence suggests heterogeneous outcomes even within the same stage. This review discusses the evolving landscape of adjuvant treatment in gastric cancer, emphasizing the transition towards precision medicine. Recent molecular characterization of gastric cancer has revealed distinct subtypes with varying prognoses and chemotherapy responses, exemplified by the favorable outcomes of microsatellite instability–high tumors without adjuvant chemotherapy. Additionally, clinical factors including sub-stages within stage II/III, patient performance status, comorbidities, and personal preferences should be considered in treatment decisions. The integration of these molecular and clinical factors, along with shared decision-making between physicians and patients, represents a crucial step toward personalized treatment approaches. Looking ahead, the field is poised for further evolution with the emergence of immune checkpoint inhibitors, growing evidence for neoadjuvant chemotherapy in selected cases, and the potential of circulating tumor DNA as a biomarker for minimal residual disease. This comprehensive approach to treatment decision-making, considering both tumor biology and patient factors, will be essential for realizing precision medicine in gastric cancer care.

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From Control to Conversion: Optimizing Systemic Therapy for Curative-Intent Conversion Surgery in Metastatic Gastric Cancer
Hye Sook Han, Sun Young Rha
Journal of Gastric Cancer.2026; 26(1): 146. CrossRef
Preoperative albumin-bilirubin grade combined with sarcopenia predicts long-term outcomes after laparoscopic gastrectomy for advanced gastric cancer
Shuangshuang Hou, Yang Yu, Nanbo Li, Wenjing Yu, Zhiyuan Dai, He Li, Lianyi Guo, Jiajun Yin, Ju Wu
BMC Gastroenterology.2025;[Epub] CrossRef
Dynamic postoperative prognosis and follow-up optimization for gastric cancer patients after neoadjuvant therapy: a multicenter retrospective study
Qing Zhong, Zhi-Quan Zhang, Kai-Ning Ye, Min-Xian Zhuang, Yu-Qin Sun, Zhi-Xin Shang-Guan, Dong Wu, Cai-Ming Weng, Meng-Qi Xue, Tao-Yuan Qiu, Yi Li, Yu-Bin Ma, Fang-Hui Ding, Yong-Hong Wang, Shi-Chao Wu, Bao-Long Li, Wei Zhao, Ji-Yun Zhu, Jun-Hua Yu, Ju Wu
Gastric Cancer.2025; 28(6): 1260. CrossRef

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Original Articles

Gastrointestinal cancer

A Machine Learning Risk Prediction Model for Gastric Cancer with SHapley Additive exPlanations: Bomi Park, Chung Ho Kim, Jae Kwan Jun, Mina Suh, Kui Son Choi, Il Ju Choi, Hyun Jin Oh; Cancer Res Treat. 2025;57(3):821-829. Published online December 16, 2024; DOI: https://doi.org/10.4143/crt.2024.843

Abstract PDF Supplementary Material PubReader ePub

Purpose
Gastric cancer (GC) prediction models hold potential for enhancing early detection by enabling the identification of high-risk individuals, facilitating personalized risk-based screening, and optimizing the allocation of healthcare resources.
Materials and Methods
In this study, we developed a machine learning-based GC prediction model utilizing data from the Korean National Health Insurance Service, encompassing 10,515,949 adults who had not been diagnosed with GC and underwent GC screening during 2013-2014, with a follow-up period of 5 years. The cohort was divided into training and test datasets at an 8:2 ratio, and class imbalance was mitigated through random oversampling.
Results
Among various models, logistic regression demonstrated the highest predictive performance, with an area under the receiver operating characteristic curve (AUC) of 0.708, which was consistent with the AUC obtained in external validation (0.669). Importantly, the outcomes were robust to missing data imputation and variable selection. The SHapley Additive exPlanations (SHAP) algorithm enhanced the explainability of the model, identifying advancing age, being male, Helicobacter pylori infection, current smoking, and a family history of GC as key predictors of elevated risk.
Conclusion
This predictive model could significantly contribute to the early identification of individuals at elevated risk for GC, thereby enabling the implementation of targeted preventive strategies. Furthermore, the integration of noninvasive and cost-effective predictors enhances the clinical utility of the model, supporting its potential application in routine healthcare settings.

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Liver cancer risk stratification using deep learning on nationwide longitudinal health screening data: a retrospective cohort study
Yewon Choi, Sungmin Cho, Changdai Gu, Chungho Kim, Bomi Park, Hwiyoung Kim
BMC Medical Informatics and Decision Making.2026;[Epub] CrossRef
Development and validation of a novel blood-based biomarker for gastric cancer triage in chronic dyspepsia
Minji Seo, Ka Man Cheung, Serene J. L. Lam, Peter Y. M. Woo, Winnie W. Y. Sung, James C. H. Chow, Ada S. M. Yip, Stephen K. K. Ng, Martin S. C. Lee, Henry H. W. Liu, Daisy M. Y. Kan, Sau Shan Kao, Harry H. Y. Yiu, David C. C. Lam
npj Digital Medicine.2026;[Epub] CrossRef
Development and validation of a prediction model for myelosuppression in lung cancer patients after platinum-based doublet chemotherapy: a multifactorial analysis approach
Xueyan Li
American Journal of Cancer Research.2025; 15(2): 470. CrossRef
Development and Validation of the Early Gastric Carcinoma Prediction Model in Post-Eradication Patients with Intestinal Metaplasia
Wulian Lin, Guanpo Zhang, Hong Chen, Weidong Huang, Guilin Xu, Yunmeng Zheng, Chao Gao, Jin Zheng, Dazhou Li, Wen Wang
Cancers.2025; 17(13): 2158. CrossRef
Field-Scale Maize Yield Estimation Using Remote Sensing with the Integration of Agronomic Traits
Shuai Bao, Yiang Wang, Shinai Ma, Huanjun Liu, Xiyu Xue, Yuxin Ma, Mingcong Zhang, Dianyao Wang
Agriculture.2025; 15(17): 1834. CrossRef
Ensemble Transfer Learning for Gastric Cancer Prediction Using Electronic Health Records in a Data-Scarce Single-Hospital Setting
Hyon Hee Kim, Ji Yeon Han, Yae Bin Lim, Young Seo Lim, Seung-In Seo, Kyung Joo Lee, Woon Geon Shin
Applied Sciences.2025; 15(23): 12428. CrossRef
Cross-Cancer Transfer Learning for Gastric Cancer Risk Prediction from Electronic Health Records
Daeyoung Hong, Jiung Kim, Jiyong Jung
Diagnostics.2025; 15(24): 3175. CrossRef

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Identifying Anti-cancer Effects and Exploring the Mechanism of an MPS1/TTK Inhibitor in Gastric Cancer: Eunseo Kim, Woo Sun Kwon, Tae Soo Kim, Jihyun Hwang, Sunghwan Kim, Sun Young Rha; Cancer Res Treat. 2025;57(3):803-820. Published online December 12, 2024; DOI: https://doi.org/10.4143/crt.2024.780

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study aimed to identify the anti-cancer effect and investigate the underlying mechanism of MPS1/TTK (monopolar spindle 1; also known as threonine tyrosine kinase) inhibitor in gastric cancer (GC) cell lines.
Materials and Methods
This study used compound-9, a highly selective MPS1/TTK inhibitor, to evaluate its anti-cancer effects on GC cell lines. Cell viability assay was performed to determine sensitivity to the inhibitor. Cell cycle analysis and apoptosis assays were performed using Flow cytometry to evaluate the effects of the inhibitor. Protein-expression levels were analyzed through western blotting after the inhibitor treatment.
Results
The Epstein-Barr virus and microsatellite-instable–high groups tended to be sensitive to the inhibitor, while the genomically stable (GS)–likely group tended to be moderate-to-resistant. In contrast, the chromosomal instability (CIN)–likely group was extremely sensitive or resistant. Within the CIN group, TP53^WT cell lines were sensitive, whereas TP53^MUT cell lines were sensitive or resistant. Upon treatment of the inhibitor, the TP53^WT-sensitive cell line underwent cell death more rapidly compared to the TP53^MUT-sensitive cell line. In contrast, the TP53^MUT-sensitive cell experienced higher levels of aneuploidy or polyploidy and underwent cell death at later time point than the TP53^WT-sensitive cell line. The TP53^MUT-resistant line can tolerate aneuploidy or polyploidy and exhibits drug resistance.
Conclusion
Our study explores the potential of an MPS1/TTK inhibitor, compound-9, as a targeted therapy in GC cells and investigates its mechanism of action.

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Analytical and clinical validation of CancerMaster, an automated targeted NGS panel, for tumor-only precision oncology
Jingmin Che, Woo Sun Kwon, Jaeyoung Kim, Erkhembayar Jadamba, Hyo Jun Han, Yuhnam Kim, Choong-kun Lee, Chan Hee Park, Ye Jin Moon, Han Byeol Mun, Hyun Cheol Chung, Sun Young Rha
Scientific Reports.2026;[Epub] CrossRef
Molecular and Phenotypic Characterization of Fluid-Derived Patient-Derived Cell and Organoid Models in Advanced Gastric Cancer
Ye Jin Moon, Woo Sun Kwon, Chan Hee Park, Jinsoo Jang, Juin Park, Byeong Gyu Yoon, Han Byeol Mun, Namju Kim, Choong-kun Lee, Hei Cheul Jeung, Su-Jin Shin, Tae Soo Kim, Sun Young Rha
Journal of Gastric Cancer.2026; 26(2): 260. CrossRef
The Status of SOX2 Expression in Gastric Cancers with Induction of CDX2 Defines Groups with Different Genomic Landscapes
Ioannis A. Voutsadakis
Genes.2025; 16(3): 279. CrossRef

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199 Download
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The Histone Deacetylase Inhibitor Entinostat Mediates HER2 Downregulation in Gastric Cancer, Providing the Basis for Its Particular Efficacy in HER2-Amplified Tumors and in Combination Therapies: Tamara Zenz, Robert Jenke, René Thieme, Tim Kahl, Hannes Borchardt, Ines Gockel, Finn K. Hansen, Achim Aigner, Thomas R. H. Büch; Cancer Res Treat. 2025;57(3):781-802. Published online December 10, 2024; DOI: https://doi.org/10.4143/crt.2024.546

Abstract PDF Supplementary Material PubReader ePub

Purpose
Human epidermal growth factor receptor 2 (HER2) inhibition represents a therapeutic approach with proven clinical efficacy in gastric cancer. However, resistance against HER2-directed therapeutics highlights the need for alternative approaches or drug combinations. Histone deacetylase inhibitors (HDACi) display a broad spectrum of antitumor properties, which may include effects on receptor tyrosine kinases.
Materials and Methods
We analyzed the effects of the class I HDACi entinostat in a panel of HER2-amplified and non-amplified gastric adenocarcinoma cells in 2D cell culture as well as in tumor slice models ex vivo and in patient-derived xenografts in vivo. Effects on protein expression/signal transduction were evaluated by immunoblotting and quantitative reverse transcription polymerase chain reaction.
Results
HDAC inhibition reduced HER2 protein expression independently of initial HER2 expression levels. This was associated with the upregulation of the HER2-inhibiting microRNA miR-205. The downregulation of HER2 resulted in reduced AKT phosphorylation, apoptosis induction and antiproliferative effects, with particularly high efficiency in HER2-amplified gastric cancer cells. Inhibiting HER2 by a specific kinase inhibitor in gastric cancer cells with low basal HER2 expression led to HER2 upregulation. This was reversed by entinostat treatment and provided the basis for synergistic cell inhibition upon double treatment.
Conclusion
We describe the downregulation of HER2 in gastric carcinoma cells upon HDACi treatment. Concomitantly, cells with high basal or treatment-induced HER2 expression showed most profound sensitivities towards HDACi. These findings may thus provide the basis for HDACi treatment as a therapeutic option particularly valuable in HER2-amplified gastric cancer and particularly useful in combination therapies with HER2 inhibitors.

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Acquired vulnerability against EGF receptor inhibition in gastric cancer promoted by class I histone deacetylase inhibitor entinostat
Tamara Zenz, Robert Jenke, Denys Oliinyk, Sandra Noske, René Thieme, Tim Kahl, Ines Gockel, Florian Meier-Rosar, Achim Aigner, Thomas RH Büch
Neoplasia.2025; 60: 101121. CrossRef

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Association of Pro-inflammatory Cytokines with Gastric Cancer Risk: A Case-Cohort Study: Seungju Baek, Eunjung Park, Eun Young Park; Cancer Res Treat. 2025;57(3):760-769. Published online November 19, 2024; DOI: https://doi.org/10.4143/crt.2024.718

Abstract PDF PubReader ePub

Purpose
This study aimed to assess the association between inflammatory cytokines and the risk of gastric cancer (GC).
Materials and Methods
We conducted a case-cohort study using Korean National Cancer Center Community (KNCCC) cohort data to investigate the associations between pro-inflammatory, anti-inflammatory cytokines, inflammatory mediators, and GC risk in the Korean general population (GC cases: n=159, subcohort: n=822). Serum levels of inflammatory cytokines were measured using Quantikine enzyme-linked immunosorbent assay and analyzed using a Cox proportional hazards regression model.
Results
Compared to those with the lowest serum interleukin 6 (IL-6) levels, the risk of GC significantly increased in the second (hazard ratio [HR], 3.48; 95% confidence interval [CI], 1.73 to 6.99), third (HR, 3.74; 95% CI, 1.91 to 7.29), and fourth quartiles (HR, 3.79; 95% CI, 1.93 to 7.48). Elevated levels of interleukin 1β (IL-1β) (HR, 1.57; 95% CI, 1.12 to 2.21) and interferon-γ (IFN-γ) (HR, 2.49; 95% CI, 1.73 to 3.58) were also associated with an increased risk of GC.
Conclusion
The findings of this study indicate associations between pro-inflammatory cytokines (IL-6, IL-1β, and IFN-γ) and the risk of GC, suggesting that regulating these cytokine levels may aid in GC prevention.

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Inflammatory Cytokines and Oxidative Stress Markers in Relation to Colorectal Cancer Risk: A Case–Cohort Study in a Korean Population
Eunjung Park, Seungju Baek, Jin-Kyoung Oh, Min Kyung Lim, Eun Young Park
Cancers.2026; 18(3): 470. CrossRef
Serum pro-inflammatory cytokines as potential biomarkers for the diagnosis of gastric carcinoma
Le Ren, Jun Liu, Ya-Yun Xu, Zhen-Wang Shi
World Journal of Clinical Oncology.2025;[Epub] CrossRef
Inflammation and detection: Rethinking the biomarker landscape in gastric cancer
Keykavous Parang, Koosha Paydary
World Journal of Clinical Oncology.2025;[Epub] CrossRef

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Presence of RB1 or Absence of LRP1B Mutation Predicts Poor Overall Survival in Patients with Gastric Neuroendocrine Carcinoma and Mixed Adenoneuroendocrine Carcinoma: In Hye Song, Bokyung Ahn, Young Soo Park, Deok Hoon Kim, Seung-Mo Hong; Cancer Res Treat. 2025;57(2):492-506. Published online September 27, 2024; DOI: https://doi.org/10.4143/crt.2024.667

Abstract PDF Supplementary Material PubReader ePub

Purpose
Neuroendocrine carcinomas (NECs) of the stomach are extremely rare, but fatal. However, our understanding of the genetic alterations in gastric NECs is limited. We aimed to evaluate genomic and clinicopathological characteristics of gastric NECs and mixed adenoneuroendocrine carcinomas (MANECs).
Materials and Methods
Fourteen gastric NECs, three gastric MANECs, and 1,381 gastric adenocarcinomas were retrieved from the departmental next-generation sequencing database between 2017 and 2022. Clinicopathological parameters and next-generation sequencing test results were retrospectively collected and reviewed.
Results
Gastric NECs and MANECs frequently harbored alterations of TP53, RB1, SMARCA4, RICTOR, APC, TOP1, SLX4, EGFR, BRCA2, and TERT. In contrast, gastric adenocarcinomas exhibited alterations of TP53, CDH1, LRP1B, ARID1A, ERBB2, GNAS, CCNE1, NOTCH, and MYC. Mutations of AKT3, RB1, and SLX4; amplification of BRCA2 and RICTOR; and deletion of ADAMTS18, DDX11, KLRC3, KRAS, MAX, NFKBIA, NUDT7, and RB1 were significantly more frequent in gastric NECs and MANECs than in gastric adenocarcinomas. The presence of LRP1B mutation was significantly associated with longer overall survival (OS), whereas RB1 mutation and advanced TNM stage were associated with shorter OS.
Conclusion
We identified frequently mutated genes and potential predictors of survival in patients with gastric NECs and MANECs.

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Malignant Hepatocellular Neoplasm, Not Otherwise Specified, Displays Poorer Chemoresponsiveness and Postoperative Prognosis Than Hepatoblastoma
In Hye Song, Sujin Gang, Hee Mang Yoon, Pyeong Hwa Kim, Bokyung Ahn, Jihun Kim, Deok Hoon Kim, Jung-Man Namgoong, Kyung-Nam Koh
Cancer Research and Treatment.2026; 58(2): 642. CrossRef
Hepatoid adenocarcinoma of the stomach and non-hepatoid alpha-fetoprotein-producing gastric cancer exhibit a high degree of molecular similarity
Liqiao Chen, Xuesong Yang, Peiyu Zhu, Han Bao, Yan Wu, Ke Ji, Ji Zhang, Xiaojiang Wu, Kai Zhou, Jieli Xu, Jiatian Tang, Anqiang Wang, Zhaode Bu
Cellular Oncology.2025;[Epub] CrossRef

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Special Article

Trends in Cancer-Screening Rates in Korea: Findings from the National Cancer Screening Survey, 2004-2023: EunKyo Kang, Kui Son Choi, Jae Kwan Jun, Yeol Kim, Hyeon Ji Lee, Chang Kyun Choi, Tae Hee Kim, Sun Hwa Lee, Mina Suh; Cancer Res Treat. 2025;57(1):28-38. Published online August 2, 2024; DOI: https://doi.org/10.4143/crt.2024.325

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study aimed to report the overall national trends in the rates of cancer screening based on recommendations and provide insights into the changing trends of these rates across different demographics.
Materials and Methods
This study used data from the Korean National Cancer Screening Survey (KNCSS), which surveys nationwide cancer-screening rates and includes 4,500 individuals meeting the Korean National Cancer Screening Program (NCSP) protocol age criteria. Cancer-screening rates were assessed using structured questionnaires; yearly trends were analyzed for both lifetime cancer-screening rates and rates of screening based on recommendations, and subgroup analyses were performed based on age and sex.
Results
The rates of cancer screening based on recommendations showed significant increments: the stomach cancer-screening rate increased from 39.2% in 2004 to 77.5% in 2023 (3.50% per year), the liver cancer-screening rate increased from 20.0% to 48.8% (4.30% per year), and the colorectal cancer, increased from 19.9% to 70.7% (5.15% per year). The breast cancer-screening rate increased from 33.2% to 72.7% (2.88% per year), and the cervical cancer, increased from 58.3% to 70.2% (1.08% per year). Despite some differences, particularly in relation to sociodemographic factors, screening rates increased significantly for all cancer types.
Conclusion
Cancer-screening rates in Korea increased consistently from 2004 to 2023, demonstrating the effectiveness of the national cancer-screening program. However, the increments in breast, cervical and lung cancer-screening rates were relatively lower, indicating the need for additional efforts and strategies.

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Optimal interval of screening endoscopy for reducing gastric cancer mortality: a nationwide cohort study
Soo-Yoon Sung, Hyun Ho Choi, Seung Ho Sin, Hyung-Keun Kim, Sang Woo Kim, Sung Soo Kim
Gastrointestinal Endoscopy.2026; 103(4): 725. CrossRef
Practice of Cytopathology in Korea: A 40‐Year Evolution Through Standardization, Digital Transformation, and Global Partnership
Yosep Chong, Ran Hong, Hyeong Ju Kwon, Haeryoung Kim, Lucia Kim, Soon Jae Kim, Yoon Jung Choi
Diagnostic Cytopathology.2026; 54(2): 146. CrossRef
Persistent income-related inequalities in cancer screening utilisation in South Korea: Evidence from repeated cross-sectional data, 2013–2023
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Jaewoo Cha, Minku Kang
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Lisa Jungblut
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Original Articles

Gastrointestinal cancer

Proximal Gastrectomy Is Associated with Lower Incidence of Anemia and Vitamin B12 Deficiency Compared to Total Gastrectomy in Patients with Upper Gastric Cancer: Jeong Ho Song, Sung Hyun Park, Minah Cho, Yoo Min Kim, Woo Jin Hyung, Hyoung-Il Kim; Cancer Res Treat. 2025;57(1):174-185. Published online July 3, 2024; DOI: https://doi.org/10.4143/crt.2024.319

Abstract PDF Supplementary Material PubReader ePub

Purpose
Proximal gastrectomy is an alternative to total gastrectomy (TG) for early gastric cancer (EGC) treatment in the upper stomach. However, its benefits in terms of perioperative and long-term outcomes remain controversial. The aim of this study was to compare the perioperative, body compositional, nutritional, and survival outcomes of patients undergoing proximal gastrectomy with double-tract reconstruction (PG-DTR) and TG for pathological stage I gastric cancer in upper stomach.
Materials and Methods
The study included 506 patients who underwent gastrectomy for pathological stage I gastric cancer in the upper stomach between 2015 and 2019. Clinicopathological, perioperative, body compositional, nutritional, and survival outcomes were compared between the PG-DTR and TG groups.
Results
The PG-DTR and TG groups included 197 (38.9%) and 309 (61.1%) patients, respectively. The PG-DTR group had a lower rate of early complications (p=0.041), lower diagnosis rate of anemia and vitamin B12 deficiency (all p < 0.001), and lower replacement rate of iron and vitamin B12 compared to TG group (all p < 0.001). The PG-DTR group showed reduced incidence of sarcopenia at 6-months postoperatively, preserved higher amount of visceral fat after surgery (p=0.032 and p=0.040, respectively), and showed a higher hemoglobin level (p=0.007). Oncologic outcomes were comparable between the groups.
Conclusion
The PG-DTR for EGC located in the upper stomach offered advantages of fewer complications, lower incidence of anemia and vitamin B12 deficiency, less decrease in visceral fat volume, and similar survival compared to TG. Consequently, PG-DTR may be considered a superior alternative treatment option to TG.

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From mechanisms to management: a comprehensive review of sarcopenia in gastric cancer
Wenhao Liu, Hongliang Cao, Xuanpeng Zhou, Luanbiao Sun, Linchun Li, Xinyuan Song, Yang Gao, Jianpeng Xing, Shuohui Gao
Frontiers in Nutrition.2026;[Epub] CrossRef
Enhancing Quality of Life of Proximal Gastrectomy: A Comprehensive Review of Anastomotic Innovations and Challenges
Linchuan Li, Dexu Zhang, Siyi Song, Shuohui Dong, Qian Xu, Guangyong Zhang, Jiankang Zhu
Cancer Medicine.2026;[Epub] CrossRef
Pancreatic atrophy after gastric cancer surgery: influencing factors and effects on BMI and quality of life
Zhaoping Li, Lianlian Cao, Hao Chen, Feng Wang, Liang Tao, Meng Wang
World Journal of Surgical Oncology.2025;[Epub] CrossRef
Proximal Gastrectomy for Upper-third Early Gastric Cancer
Guanhong Min, Kwangyong Kim, Seonghoon Cho, Jaewoo Shim
Journal of Digestive Cancer Research.2024; 12(2): 68. CrossRef

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Varlitinib and Paclitaxel for EGFR/HER2 Co-expressing Advanced Gastric Cancer: A Multicenter Phase Ib/II Study (K-MASTER-13): Dong-Hoe Koo, Minkyu Jung, Yeul Hong Kim, Hei-Cheul Jeung, Dae Young Zang, Woo Kyun Bae, Hyunki Kim, Hyo Song Kim, Choong-kun Lee, Woo Sun Kwon, Hyun Cheol Chung, Sun Young Rha; Cancer Res Treat. 2024;56(4):1136-1145. Published online April 29, 2024; DOI: https://doi.org/10.4143/crt.2023.1324

Abstract PDF Supplementary Material PubReader ePub

Purpose
Varlitinib is a pan-human epidermal growth factor receptor (HER) inhibitor targeting epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), and HER4. We present a phase Ib/II study of a combination of varlitinib and weekly paclitaxel as a second-line treatment for patients with EGFR/HER2 co-expressing advanced gastric cancer (AGC).
Materials and Methods
Patients whose tumors with EGFR and HER2 overexpression by immunohistochemistry (≥ 1+) were enrolled. Varlitinib and paclitaxel were investigated every 4 weeks. After determining the recommended phase II dose (RP2D) in phase Ib, a phase II study was conducted to evaluate the antitumor activity.
Results
RP2D was treated with a combination of varlitinib (300 mg twice daily) and paclitaxel. Among 27 patients treated with RP2D, the median progression-free survival and overall survival (OS) were 3.3 months (95% confidence interval [CI], 1.7 to 4.9) and 7.9 months (95% CI, 5.0 to 10.8), respectively, with a median follow-up of 15.7 months. Among 16 patients with measurable disease, the objective response rate (ORR) and disease control rate were 31% and 88%, respectively. Patients with strong HER2 expression (n=8) had a higher ORR and longer OS, whereas those with strong EGFR expression (n=3) had poorer outcomes. The most common adverse events (AEs) of any grade were neutropenia (52%), diarrhea (27%), aspartate aminotransferase/alanine transaminase elevation (22%), and nausea (19%). No treatment-related deaths or unexpected AEs resulting from treatment cessation were observed in patients with RP2D.
Conclusion
A combination of varlitinib and paclitaxel displayed manageable toxicity and modest antitumor activity in patients with EGFR/HER2 co-expressing AGC who progressed after first-line chemotherapy.

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Human Epidermal Growth Factor Receptor 2 Positive Advanced Gastric or Esophagogastric Adenocarcinoma: Reflecting on the Past to Gain a New Insights
Yu Aoki, Izuma Nakayama, Kohei Shitara
Current Oncology Reports.2025; 27(1): 15. CrossRef
Pharmacotherapy for previously treated gastric cancer patients: current options and future developments
Seiya Sato, Izuma Nakayama, Kohei Shitara
Expert Review of Clinical Pharmacology.2025; 18(8): 607. CrossRef
Unraveling the future: Innovative design strategies and emerging challenges in HER2-targeted tyrosine kinase inhibitors for cancer therapy
Sixiang Zheng, Ruixian Chen, Lele Zhang, Lun Tan, Lintao Li, Fangyi Long, Ting Wang
European Journal of Medicinal Chemistry.2024; 276: 116702. CrossRef

5,570 View
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Effector Function Characteristics of Exhausted CD8+ T-Cell in Microsatellite Stable and Unstable Gastric Cancer: Dong-Seok Han, Yoonjin Kwak, Seungho Lee, Soo Kyung Nam, Seong-Ho Kong, Do Joong Park, Hyuk-Joon Lee, Nak-Jung Kwon, Hye Seung Lee, Han-Kwang Yang; Cancer Res Treat. 2024;56(4):1146-1163. Published online April 12, 2024; DOI: https://doi.org/10.4143/crt.2024.317

Abstract PDF PubReader ePub

Purpose
Gastric cancer exhibits molecular heterogeneity, with the microsatellite instability–high (MSI-H) subtype drawing attention for its distinct features. Despite a higher survival rate, MSI-H gastric cancer lack significant benefits from conventional chemotherapy. The immune checkpoint inhibitors, presents a potential avenue, but a deeper understanding of the tumor immune microenvironment of MSI-H gastric cancer is essential.
Materials and Methods
We explored the molecular characteristics of CD8+ T-cell subtypes in three MSI-H and three microsatellite stable (MSS) gastric cancer samples using single-cell RNA sequencing and spatial transcriptome analysis.
Results
In MSI-H gastric cancer, significantly higher proportions of effector memory T cell (Tem), exhausted T cell (Tex), proliferative exhausted T cell (pTex), and proliferative T cell were observed, while MSS gastric cancer exhibited significantly higher proportions of mucosal-associated invariant T cell and natural killer T cell. In MSI-H gastric cancer, Tex and pTex exhibited a significant upregulation of the exhaustion marker LAG3, as well as elevated expression of effector function markers such as IFNG, GZMB, GZMH, and GZMK, compared to those in MSS gastric cancer. The interferon γ (IFN-γ) signaling pathway of Tex and pTex was retained compared to those of MSS gastric cancer. The spatial transcriptome analysis demonstrates the IFN-γ signaling pathway between neighboring Tex and malignant cell, showcasing a significantly elevated interaction in MSI-H gastric cancer.
Conclusion
Our study reveals novel finding indicating that IFN-γ signaling pathway is retained in Tex and pTex of MSI-H gastric cancer, offering a comprehensive perspective for future investigations into immunotherapy for gastric cancer.

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Gallic acid potentiates the tumour-killing function of CD8+ T cells in gastric cancer
Si Chen, HaiBin Wang, Meixu Lei, Yumin Li, Qi Wang, Hengxin Wang, Yifei Shen, Xuejie Su, Yali Zhou
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Exploring the molecular pathology and tumor microenvironment in gastric cancer liver metastasis
Jialu Zhuang, Chao Hu, Lei Lei, Yimeng Sang, Qi Sun, Hongping Xia
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Hongfei Yan, Yang Liu
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Dongjie Ye, Zhu Zhang, Yuxin Yao, Banglun Pan, Hao Wu, Xinyu Zhang, Xiaoqian Wang, Nanhong Tang
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Hangping Wei, Xiaowei Zhang, Zhen Zhou, Jianbin Xie, Weidong Han, Xiaofang Dong
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Simvastatin induces ferroptosis and activates anti-tumor immunity to sensitize anti-PD-1 immunotherapy in microsatellite stable gastric cancer
Yumei Ning, Shilin Fang, Runan Zhang, Jun Fang, Kun Lin, Yang Ding, Haihang Nie, Jingkai Zhou, Qiu Zhao, Hengning Ke, Haizhou Wang, Fan Wang
International Immunopharmacology.2024; 142: 113244. CrossRef

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General

Phase 1/2a Study of Rivoceranib, a Selective VEGFR-2 Angiogenesis Inhibitor, in Patients with Advanced Solid Tumors: Yoon-Koo Kang, Min-Hee Ryu, Yong Sang Hong, Chang-Min Choi, Tae Won Kim, Baek-Yeol Ryoo, Jeong Eun Kim, John R. Weis, Rachel Kingsford, Cheol Hee Park, Seong Jang, Arlo McGinn, Theresa L. Werner, Sunil Sharma; Cancer Res Treat. 2024;56(3):743-750. Published online January 18, 2024; DOI: https://doi.org/10.4143/crt.2023.980

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study aimed to report the results from an early-phase study of rivoceranib, an oral tyrosine kinase inhibitor highly selective for vascular endothelial growth factor receptor 2, in patients with advanced solid tumors.
Materials and Methods
In this open-label, single-arm, dose-escalating, multicenter three-part phase 1/2a trial, patients had advanced solid tumors refractory to conventional therapy. Part 1 evaluated the safety and pharmacokinetics of five ascending once-daily doses of rivoceranib from 81 mg to 685 mg. Part 2 evaluated the safety and antitumor activity of once-daily rivoceranib 685 mg. Part 3 was conducted later, due to lack of maximum tolerated dose determination in part 1, to evaluate the safety and preliminary efficacy of once-daily rivoceranib 805 mg in patients with unresectable or advanced gastric cancer.
Results
A total of 61 patients were enrolled in parts 1 (n=25), 2 (n=30), and 3 (n=6). In parts 1 and 2, patients were white (45.5%) or Asian (54.5%), and 65.6% were male. The most common grade ≥ 3 adverse events were hypertension (32.7%), hyponatremia (10.9%), and hypophosphatemia (10.9%). The objective response rate (ORR) was 15.2%. In part 3, dose-limiting toxicities occurred in two out of six patients: grade 3 febrile neutropenia decreased appetite, and fatigue. The ORR was 33%.
Conclusion
The recommended phase 2 dose of rivoceranib was determined to be 685 mg once daily, which showed adequate efficacy with a manageable safety profile (NCT01497704 and NCT02711969).

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Advances in Targeted and Systemic Therapy for Salivary Gland Carcinomas: Current Options and Future Directions
Sushanth Sreenivasan, Rahim Jiwani, Richard White, Veli Bakalov, Ryan Moll, Joseph Liput, Larisa Greenberg
Current Oncology.2025; 32(4): 232. CrossRef
Proteomics profiling reveals the potential targets of Apatinib inhibiting the proliferation of glioma U251 cell
Yuyu Zhang, Yunshan Li, Fang Xu, Liangyu Pan, Saihang Zhang, Panpan Zhang, Xia Qin, Zuxiao Yang, Wei Yang, Wei Zhang, Dezhi Kong
Biochemical and Biophysical Research Communications.2025; 775: 152148. CrossRef

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Gastrointestinal cancer

NESC Multicenter Phase II Trial in the Preoperative Treatment of Gastric Adenocarcinoma with Chemotherapy (Docetaxel-Cisplatin-5FU+Lenograstim) Followed by Chemoradiation Based 5FU and Oxaliplatin and Surgery: Laurent Mineur, Frederi Plat, Françoise Desseigne, Gael Deplanque, Mohamed Belkacemi, Laurence Moureau-Zabotto, Carlos D. Beyrne, Khadija Jalali, Stéphane Obled, Denis Smith, Léa Vazquez, Rania Boustany; Cancer Res Treat. 2024;56(2):580-589. Published online October 5, 2023; DOI: https://doi.org/10.4143/crt.2023.812

Abstract PDF Supplementary Material PubReader ePub

Purpose
Preoperative chemoradiation (CRT) is expected to increase the rate of curative resection and complete histological response. In this trial, we investigated the efficacy of a neoadjuvant CRT regimen in gastric adenocarcinoma (NCT01565109 trial).
Materials and Methods
Patients with stage IB to IIIC gastric adenocarcinoma, endoscopy ultrasound and computed tomography–scan diagnosed, were eligible for this phase II trial. Neoadjuvant treatment consisted of 2 cycles of chemotherapy with DCF (docetaxel, cisplatin, and 5-fluorouracil [5FU]) followed by preoperative CRT with oxaliplatin, continuous 5FU and radiotherapy (45 Gy in 25 fractions of 1.8 Gy, 5 fractions per week for 5 weeks) administered before surgery. R0-resection rate, pathological complete response (pathCR) rate, and survival (progression-free survival [PFS] and overall survival [OS]) were evaluated as primary endpoints.
Results
Among 33 patients included, 32 patients (97%) received CRT and 26 (78.8%) were resected (R0 resection for all patients resected). Among resected patients, we report pathCR in 23,1% and pathologic major response (tumor regression grade 2 according to Mandard’s classification) in 26,9%. With a median follow-up duration of 5.82 years (range, 0.4 to 9.24 years), the estimated median OS for all 33 patients was not reached; 1-, 3-, and 5-year OS rates were 85%, 61%, and 52%, respectively. Among resected patients, those whose histological response was tumor grade regression (TRG) 1-2 had significantly better OS and PFS rates than those with a TRG 3-4-5 response (p=0.019 and p=0.016, respectively).
Conclusion
Promising results from trials involving preoperative chemoradiation followed by surgery in gastric cancer need to be further evaluated in a phase III trial.

Citations

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The association between pathological complete response and prognosis of gastric or adenocarcinoma of esophagogastric junction cancer following neoadjuvant chemotherapy: A meta-analysis
Yuwei Cao, Tao Jin, Zehua Chen, Ershuo Du, Panping Liang, Yining Gou, Kun Yang
European Journal of Surgical Oncology.2026; 52(1): 110528. CrossRef
Neoadjuvant Chemoradiotherapy in Locally Advanced Gastric Adenocarcinoma: Long-Term Results and Statistical Algorithm to Predict Individual Risk of Relapse
Miguel Ortego, Olast Arrizibita, Adriana Martinez-Lage, Ángel Vizcay Atienza, Laura Álvarez Gigli, Oskitz Ruiz, José Carlos Subtil, Maialen Zabalza, Victor Valentí, Ana Tortajada, María José Hidalgo, Onintza Sayar, Javier Rodriguez
Cancers.2025; 17(9): 1530. CrossRef
Efficacy of Cisplatin-Containing Chemotherapy Regimens in Patients of Pancreatic Ductal Adenocarcinoma: A Systematic Review and Meta-analysis
Obaid Ur Rehman, Eeshal Fatima, Zain Ali Nadeem, Arish Azeem, Jatin Motwani, Habiba Imran, Hadia Mehboob, Alishba Khan, Omer Usman
Journal of Gastrointestinal Cancer.2024; 55(2): 559. CrossRef
The Comparison of FLOT and DCF Regimens as Perioperative Treatment for Gastric Cancer
Gökhan Uçar, Serhat Sekmek, İrfan Karahan, Yakup Ergün, Özlem Aydın İsak, Sezai Tunç, Mutlu Doğan, Fatih Gürler, Doğan Bayram, Yusuf Açıkgöz, Selin Aktürk Esen , Burak Civelek, Fahriye Tuğba Köş , Öznur Bal, Efnan Algın, Tülay Eren, Gökşen İnanç İmamoğ
Oncology.2024; : 1. CrossRef

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Genomic and Transcriptomic Characterization of Gastric Cancer with Bone Metastasis: Sujin Oh, Soo Kyung Nam, Keun-Wook Lee, Hye Seung Lee, Yujun Park, Yoonjin Kwak, Kyu Sang Lee, Ji-Won Kim, Jin Won Kim, Minsu Kang, Young Suk Park, Sang-Hoon Ahn, Yun-Suhk Suh, Do Joong Park, Hyung Ho Kim; Cancer Res Treat. 2024;56(1):219-237. Published online August 11, 2023; DOI: https://doi.org/10.4143/crt.2023.340

Abstract PDF Supplementary Material PubReader ePub

Purpose
Bone metastasis (BM) adversely affects the prognosis of gastric cancer (GC). We investigated molecular features and immune microenvironment that characterize GC with BM compared to GC without BM.
Materials and Methods
Targeted DNA and whole transcriptome sequencing were performed using formalin-fixed paraffin-embedded primary tumor tissues (gastrectomy specimens) of 50 GC cases with distant metastases (14 with BM and 36 without BM). In addition, immunohistochemistry (IHC) for mucin-12 and multiplex IHC for immune cell markers were performed.
Results
Most GC cases with BM had a histologic type of poorly cohesive carcinoma and showed worse overall survival (OS) than GC without BM (p < 0.05). GC with BM tended to have higher mutation rates in TP53, KDR, APC, KDM5A, and RHOA than GC without BM. Chief cell-enriched genes (PGA3, PGC, and LIPF), MUC12, MFSD4A, TSPAN7, and TRIM50 were upregulated in GC with BM compared to GC without BM, which was correlated with poor OS (p < 0.05). However, the expression of SERPINA6, SLC30A2, PMAIP1, and ITIH2 were downregulated in GC with BM. GC with BM was associated with PIK3/AKT/mTOR pathway activation, whereas GC without BM showed the opposite effect. The densities of helper, cytotoxic, and regulatory T cells did not differ between the two groups, whereas the densities of macrophages were lower in GC with BM (p < 0.05).
Conclusion
GC with BM had different gene mutation and expression profiles than GC without BM, and had more genetic alterations associated with a poor prognosis.

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Bangxing Lin, Shizheng Tong, Chaokai Ba, Xiang Wang
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Wei Qiu, Ke Zhang, Wei Hu, DongSheng Liu
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