Cancer Research and Treatment

Efficacy and Safety of Ifosfamide and Mesna in Metastatic Castration-Resistant Prostate Cancer after Taxane-Based Chemotherapy and Novel Hormonal Therapy Failure: Chang Gon Kim, Yeo Gyeong Ko, Jongjin Yoon, Chung Lee, Seung Hoon Beom, Young-Deuk Choi, Woong Kyu Han, Won Sik Ham, Hyunho Han, Jongsoo Lee, Ji Eun Heo, Daeseong Kim, Eun Sil Baek, Sangwoo Kim, Minsun Jung, Sang Joon Shin; Received February 10, 2025 Accepted June 8, 2025 Published online June 9, 2025; DOI: https://doi.org/10.4143/crt.2025.155 [Accepted]

Abstract PDF: Purpose
Limited treatment options exist for patients with metastatic castration-resistant prostate cancer (mCRPC) after the failure of taxane-based chemotherapy and novel hormonal therapy. Here, we report the safety and efficacy of ifosfamide and mesna in patients with mCRPC after the failure of taxane-based chemotherapy and novel hormonal therapy (NCT06236789).
Materials and Methods
Patients with histologically confirmed prostate cancer who had failed taxane-based chemotherapy and novel hormonal therapy received ifosfamide 2,500 mg/m² and mesna 1,500 mg/m² on days 1–3, repeated every 21 days. Safety, objective response rate, disease control rate, reduction in serum prostate-specific antigen (PSA) concentration by >50% (PSA₅₀) or >90% (PSA₉₀), radiographic progression-free survival (rPFS), and overall survival (OS) were analyzed.
Results
A total of 47 patients with mCRPC were included in the study. The median number of lines of treatment was 5 (range: 3–7). All patients were previously administered docetaxel and novel hormonal therapies including abiraterone (51.1%) and/or enzalutamide (61.7%). Thirty-eight patients (80.9%) were administered cabazitaxel. The objective response and disease control rates were 21.3% and 80.9%, respectively. PSA₅₀ and PSA₉₀ were achieved in 31.9% and 10.6%, respectively. During a median follow-up duration of 54.3 months, rPFS and OS were 5.0 and 9.0 months, respectively. All the patients experienced treatment-related adverse events of any grades; however, no new safety signs were detected. Genomic biomarker analysis revealed that alterations in the TP53 pathway were associated with inferior rPFS and OS.
Conclusion
Ifosfamide and mesna showed appreciable efficacy and manageable safety profiles in heavily treated patients with mCRPC.

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Real-world Efficacy of Intravesical Gemcitabine for BCG-Unresponsive Non-Muscle-Invasive Bladder Cancer: Hye Won Lee, Eui Hyun Jung, Kyung Hwan Kim, Hong Koo Ha, Jong Jin Oh, Seok Ho Kang, Seung-hwan Jeong, Hyeong Dong Yuk, Ji Eun Heo, Won Sik Ham, Eu Chang Hwang, Seung Il Jung, Wan Song, Bumjin Lim, Bumsik Hong, Byung Chang Jeong, Ho Kyung Seo; Received January 23, 2025 Accepted May 11, 2025 Published online May 12, 2025; DOI: https://doi.org/10.4143/crt.2025.100 [Accepted]

Abstract PDF: Purpose
This study aimed to report the real-world outcomes of intravesical gemcitabine for bacillus Calmette–Guérin (BCG) -unresponsive, high-risk, non-muscle-invasive bladder cancer (HR-NMIBC) in Korean patients who were unable or unwilling to undergo radical cystectomy (RC).
Materials and Methods
This retrospective study included 131 patients (median age: 69 years; 89% men) treated with intravesical gemcitabine for BCG-unresponsive HR-NMIBC at nine centers between May 2019 and April 2022. The primary endpoint was 1-year recurrence-free survival (RFS). The secondary endpoints included factors influencing RFS, progression-free survival (PFS), cystectomy-free survival, cancer-specific survival (CSS), overall survival (OS), and safety. Survival analysis was performed using the Kaplan–Meier method, and risk factors for recurrence were assessed using Cox regression models.
Results
Patients were followed up for a median duration of 25 months, with carcinoma in situ (CIS) in 42% of the patients. The 1-year and 2-year RFS rates were 68% and 42%, while the 1-year and 2-year PFS rates were 87% and 77%, respectively. No significant factors influencing RFS were identified. Seventeen patients underwent RC during a median follow-up of 16 months, with the condition in three patients progressing to muscle-invasive disease on final pathological analysis. The 2-year CSS and OS rates were 98% and 97%, respectively. Intravesical gemcitabine was well-tolerated, with only 7 patients (5.3%) unable to complete the full induction course.
Conclusion
Our research highlights the potential of intravesical gemcitabine as a viable bladder-sparing treatment option for BCG-unresponsive HR-NMIBC, providing real-world evidence on its safety, efficacy, and tolerability.

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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; Received February 5, 2025 Accepted April 17, 2025 Published online April 18, 2025; DOI: https://doi.org/10.4143/crt.2025.135 [Accepted]

Abstract PDF: 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 Method
RASSF4 expression was analyzed in 13 cancer cell lines and 20 carcinoma tissues using PCR 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 8 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-FU. 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 Impact of Obesity on Treatment Outcomes in Patients with Hormone Receptor-Positive HER2-Negative Metastatic Breast Cancer Receiving CDK 4/6 Inhibitors: Yoo Bin Jung, Hee Kyung Ahn, Hyun-Young Shin, Ji Hyung Hong, Chai Hong Rim; Received January 25, 2025 Accepted April 13, 2025 Published online April 15, 2025; DOI: https://doi.org/10.4143/crt.2025.110 [Accepted]

Abstract PDF: Purpose
Guidelines from the aromatase inhibitor era for early breast cancer (EBC) treatment recommend maintaining a body mass index (BMI) below 25. In the current era of CDK 4/6 inhibitors, now standard in metastatic breast cancer (MBC), limited data exist on treatment outcomes in obese patients. This study investigates how adiposity affects the treatment outcome of CDK 4/6 inhibitors in patients with hormone receptor (HR)-positive, HER2-negative MBC.
Materials and Methods
We searched PubMed, MEDLINE, and Embase databases, assessing efficacy outcomes such as progression-free survival (PFS) based on obesity markers, including BMI and visceral adipose tissue (VAT) index.
Results
Twelve studies were reviewed, with seven studies and 1,812 patients included in a pooled meta-analysis. Among patients with BMI ≥25, modest improvement in PFS was observed, with a pooled hazard ratio (HR) of 0.944 (95% CI, 0.909-0.980; p = 0.003). Besides, add-on analysis using VAT to define obesity revealed a notable PFS improvement, with a pooled HR of 0.452 (95% CI, 0.256-0.798; p = 0.006).
Conclusion
While BMI-defined obesity showed slight PFS improvement with CDK 4/6 inhibitors and endocrine therapy, using VAT to define obesity revealed significant PFS gains. This highlights the need for further research on biomarker to clarify the role of adiposity in MBC, which may differ from its impact in EBC.

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Spatial Transcriptomic Landscape of Brain Metastases from Triple-Negative Breast Cancer: Comparison of Primary Tumor and Brain Metastases Using Spatial Analysis: Jihwan Yoo, Inho Park, Hyun Jung Kim, Hun Ho Park, Sora Lee, Jee Hung Kim, Yoon Jin Cha; Received January 8, 2025 Accepted April 13, 2025 Published online April 15, 2025; DOI: https://doi.org/10.4143/crt.2025.033 [Accepted]

Abstract PDF: Purpose
Triple-negative breast cancer (TNBC) is a particularly aggressive subtype of breast cancer, with approximately 30% of patients eventually developing brain metastases (BM), which result in poor outcomes. An understanding of the tumor microenvironment (TME) at both primary and metastatic sites offers insights into the mechanisms underlying BM and potential therapeutic targets.
Materials and Method
Spatial RNA sequencing (spRNA-seq) was performed on primary TNBC and paired BM tissues from three patients, one of whom had previously received immune checkpoint inhibitors before BM diagnosis. Specimen regions were categorized into tumor, proximal, and distal TME based on their spatial locations. Gene expression differences across these zones were analyzed, and immune cell infiltration was estimated using TIMER. A gene module analysis was conducted to identify key gene clusters associated with BM.
Results
Distinct gene expression profiles were noted in the proximal and distal TMEs. In BM, the proximal TME exhibited neuronal gene expression, suggesting neuron-tumor interactions compared to tumor, and upregulation of epithelial genes compared to the distal TME. Immune cell analysis revealed dynamic changes in CD8+ T cells and macrophages across the tumor and TME zones. Gene module analysis identified five key modules, including one related to glycolysis, which correlated with patient survival. Drug repurposing analysis identified potential therapeutic targets, including VEGFA, RAC1, EGLN3, and CAMK1D.
Conclusion
This study provides novel insights into the transcriptional landscapes in TNBC BM using spRNA-seq, emphasizing the role of neuron-tumor interactions and immune dynamics. These findings suggest new therapeutic strategies and underscore the importance of further research.

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Comparison of Long-term Oncological Outcome of Sentinel Lymph Node Mapping Methods (Dye-Only versus Dye and Radioisotope) in Breast Cancer Patients Following Neoadjuvant Chemotherapy: Jinyoung Byeon, Changjin Lim, Eunhye Kang, Ji-Jung Jung, Hong-Kyu Kim, Han-Byoel Lee, Hyeong-Gon Moon, Wonshik Han; Received December 30, 2024 Accepted April 13, 2025 Published online April 15, 2025; DOI: https://doi.org/10.4143/crt.2024.1253 [Accepted]

Abstract PDF: Purpose
Sentinel lymph node biopsy (SLNB) using dye and isotope (DUAL) is recommended over the dye-only (DYE) method after neoadjuvant chemotherapy (NCT) due to potentially lower false-negative rates. However, the long-term outcome of either method is unclear. We aimed to compare the long-term oncological outcomes of DYE versus DUAL SLNB methods in patients who received NCT.
Materials and Methods
In this retrospective cohort study, 893 patients who underwent SLNB following NCT and had pathologically negative lymph nodes were included. After propensity score matching for cT, cN, and pT stages, 280 patients were in the DYE group and 560 in the DUAL group. Indigo carmine was used for dye and Tc-99m antimony trisulfate for isotope mapping.
Results
Median follow-up was 75.6 months in the DYE group and 83.0 months in the DUAL group. Mean (±SD) number of harvested sentinel nodes was 6.7 (±3.4) and 6.7 (±3.8) in the DYE and DUAL groups (p=0.51). Five-year distant metastasis-free survival was 95.2% in DYE group and 93.3% in DUAL group (HR=1.45; 95% CI, 0.82–2.57; p=0.19). Disease-free survival (HR=0.97; 95% CI, 0.69–1.50; p=0.91) and overall survival (HR=0.98; 95% CI, 0.56–1.69; p=0.95) were not significantly different. Axillary recurrence rate was 1.8% and 2.5% in DYE and DUAL groups(p=0.64).
Conclusion
Long-term oncological outcomes did not significantly differ between DYE and DUAL SLNB methods. The dye-only method can be safely recommended for breast cancer patients who received NCT.

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Validation of 2023 FIGO Stage IA1–IIIC2 Endometrial Carcinoma: A Retrospective Analysis of Two Tertiary Centers in South Korea and Taiwan: Myeong-Seon Kim, Yen-Ling Lai, Yurimi Lee, Hyun-Soo Kim, Yu-Li Chen, Yoo-Young Lee; Received December 11, 2024 Accepted February 10, 2025 Published online February 17, 2025; DOI: https://doi.org/10.4143/crt.2024.1190 [Accepted]

Abstract PDF: Purpose
As understanding of the molecular pathogenesis of endometrial carcinoma (EC) advanced, the International Federation of Gynecology and Obstetrics (FIGO) staging system was revised in 2023. This study compared EC survival outcomes using the 2009 and 2023 FIGO staging systems.
Materials and Methods
We retrospectively analyzed 3,029 patients diagnosed with 2009 FIGO stage I–III EC between 1985 and 2022 in South Korea, and between 2020 and 2022 in Taiwan. All patients were reclassified using the 2023 FIGO staging, and survival and risk factors were examined under both systems.
Results
Transitioning from the 2009 to 2023 FIGO resulted in 549 (18.0%) patients being upstaged and their survival curves being diversified, indicating significant prognostic value of the 2023 FIGO. Re-classification using the 2023 FIGO upstaged the 2009 FIGO stage IA high-risk ECs, allowing more intensive treatment and potentially improving survival outcomes. The most significant changes occurred in the 2009 FIGO stages IA, IB, and IIIA ECs: upstaging in 16.5%, 49.0%, and 2.0% of IA, IB, and IIIA tumors, respectively, and downstaging 0.3% and 40.8% of IB and IIIA tumors, respectively. The risk factors for poor survival included old age (≥60), menopause, diabetes, substantial lymphovascular space invasion, aberrant p53 expression, and some aggressive histological types (carcinosarcoma, undifferentiated carcinoma, mesonephric-like adenocarcinoma, and neuroendocrine carcinoma).
Conclusion
The 2023 FIGO staging provides more refined stratification of early-stage EC than the 2009 version. Thus, the 2023 FIGO may more accurately guide prognosis and therapeutic decision-making.

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Evaluation of Nomenclature of Fatty Liver Disease in Association with Hepatocellular Carcinoma: A 14.5-Year Cohort Study in Korea: Tung Hoang, Jeonghee Lee, Bo Hyun Kim, Yuri Cho, Jeongseon Kim; Received September 7, 2024 Accepted February 10, 2025 Published online February 11, 2025; DOI: https://doi.org/10.4143/crt.2024.876 [Accepted]

Abstract PDF

Purpose
New nomenclature has incorporated metabolic traits and/or alcohol intake history to replace nonalcoholic fatty liver disease (NAFLD). Concerning the performance of different terminologies in Asian population, this study aimed to investigate the risk of developing hepatocellular carcinoma (HCC) in persons meeting the criteria for subclasses of fatty liver disease.
Materials and Methods
Between 2002 and 2021, 28,749 participants from the cancer registry linkage, who had no prior history of HCC, were prospectively included. Fatty liver disease was defined using abdominal sonography and fatty liver index. Participants were classified as having NAFLD, metabolic dysfunction–associated fatty liver disease (MAFLD), metabolic dysfunction-associated steatotic liver disease (MASLD), steatotic liver disease with increased alcohol intake (MetALD), or alcohol-related liver disease (ALD) and their association with HCC risk was investigated using Cox regression models.
Results
During a median follow-up of 14.5 years, 166 HCC cases were newly diagnosed. The prevalences of NAFLD and MASLD were 19.7% and 18.7%, respectively, whereas MAFLD was observed in 35.2% of the study population. Given the low proportion of excessive alcohol consumption, we identified 3.3% MetALD and 3.5% ALD cases. Overall, MAFLD was suggestively associated with HCC risk (hazard ratio, 1.40; 95% confidence interval 0.99-1.98). In contrast, the results for other nomenclature were not significant.
Conclusion
Our results suggest the importance of both fatty liver and the presence of metabolic dysfunction in relation to HCC risk and the need to reconsider alcohol intake thresholds in the diagnostic criteria for NAFLD and MASLD within the Korean population.

Citations

Citations to this article as recorded by

Dual etiology vs. MetALD: how MAFLD and MASLD address liver diseases coexistence
Shadi Zerehpooshnesfchi, Amedeo Lonardo, Jian-Gao Fan, Reda Elwakil, Tawesak Tanwandee, Munira Y. Altarrah, Necati Örmeci, Mohammed Eslam
Metabolism and Target Organ Damage.2025;[Epub] CrossRef
Comment on " posttreatment FIB-4 score change predicts hepatocellular carcinoma in chronic hepatitis C patients: Findings from the Taiwan hepatitis C registry program"
Junwei Guo, Dongsheng Huang
Journal of the Formosan Medical Association.2025;[Epub] CrossRef
MAFLD vs. MASLD: a year in review
Mingqian Jiang, Amna Subhan Butt, Ian Homer Cua, Ziyan Pan, Said A Al-Busafi, Nahum Méndez-Sánchez, Mohammed Eslam
Expert Review of Endocrinology & Metabolism.2025; : 1. CrossRef

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Stereotactic Ablative Radiotherapy Versus Surgery in Patients with Pulmonary Metastases from Colorectal Cancer: Byung min Lee, Ha Eun Kim, Young Ho Yang, Seung Yoon Yang, Han Sang Kim, Seo Hee Choi, Woong Sub Koom, Byung Jo Park, Jee Suk Chang; Received October 29, 2024 Accepted February 5, 2025 Published online February 6, 2025; DOI: https://doi.org/10.4143/crt.2024.1040 [Accepted]

Abstract PDF: Purpose
We compared the local control rate and toxicity of stereotactic ablative radiotherapy (SABR) versus wedge resection for colorectal pulmonary metastases.
Materials and Methods
We retrospectively reviewed medical charts and imaging of patients treated with SABR or wedge resection between 2010 and 2017 at a single institution.
Results
There were 404 patients who were treated with local therapy for 528 pulmonary metastatic lesions. While surgery was frequently used upfront for smaller, solitary metastases without other site involvement, SABR was often used for larger, multiple lesions and disease burdens beyond the lungs. The 3-year local control rate was 88.6% following surgery, which was not significantly different from that with SABR at 86.7% (p=0.174). No major postoperative complications or mortality were observed in the surgery group, and 2.8% of patients in the SABR group experienced grade 3-4 radiation pneumonitis.
Conclusion
SABR was used in patients with a higher risk of progression compared to those undergoing surgery, yet it has similar local control rates to wedge resection.

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Prognostic Value of POST-Treatment Extent of Tumor (POSTTEXT) System in Patients with Hepatoblastoma: Hana Jeong, Hee Mang Yoon, Pyeong Hwa Kim, Ah Young Jung, Young Ah Cho, Jin Seong Lee, Kyung-Nam Koh, Jung-Man Namgoong; Received June 28, 2024 Accepted January 19, 2025 Published online January 20, 2025; DOI: https://doi.org/10.4143/crt.2024.600 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub: Purpose
This study aimed to assess prognostic values of the POST-Treatment Extent of Tumor (POSTTEXT) system and clinical factors after neoadjuvant chemotherapy in hepatoblastoma patients and evaluate benefits of post-treatment imaging and clinical factors concomitant with Children’s Hepatic Tumors International Collaboration–Hepatoblastoma Stratification (CHIC-HS) system.
Materials and Methods
This single-center retrospective study of hepatoblastoma cases (2006-2022) included pediatric patients receiving ≥ 4 cycles of neoadjuvant chemotherapy, with pre- and post-treatment imaging and complete medical records. Clinical data included age, sex, and serum α-fetoprotein (AFP) levels. Cox regression analyses identified predictors of event-free survival (EFS). Time-dependent receiver operating characteristic curves assessed the predictive power of combining the CHIC-HS risk stratification with post-treatment factors. Inter-reader agreement was analyzed using weighted kappa.
Results
Among the 109 hepatoblastoma patients, 73 (mean age, 2.2±2.7 years) met the inclusion criteria. Prognostic factors for EFS included AFP levels after the fourth cycle of neoadjuvant chemotherapy (hazard ratio [HR], 1.233; 95% confidence interval [CI], 1.086 to 1.400; p=0.001), tumor size change ratio (HR, 0.654; 95% CI, 0.448 to 0.955; p=0.030), and POSTTEXT annotation factor M (HR, 5.209; 95% CI, 1.639 to 16.553; p=0.005). Incorporating AFP levels after the fourth cycle of neoadjuvant chemotherapy into the CHIC-HS improved predictive power (p=0.043). POSTTEXT system showed better inter-reader agreement than PRE-Treatment Extent of tumor (PRETEXT).
Conclusion
Predictors of EFS in hepatoblastoma include AFP levels after the fourth cycle of neoadjuvant chemotherapy, tumor size change ratio, and metastasis (POSTTEXT M). Combining AFP levels after the fourth cycle of neoadjuvant chemotherapy to the CHIC-HS improved the predictive ability.

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Lipid Metabolism Related Gene ACSL3 as a Biomarker for Predicting Immunotherapy Outcomes in Lung Adenocarcinoma: Taiping He, Jinhan Hu, Haoyue Guo, Meng Diao, Yuanyuan Wang, Yuhan Wu, Lei Cheng, Chao Zhao, Xuefei Li, Caicun Zhou; Received November 22, 2024 Accepted January 16, 2025 Published online January 20, 2025; DOI: https://doi.org/10.4143/crt.2024.1119 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub: Purpose
Investigate the role of lipid metabolism in the tumor immune microenvironment (TIME) of lung adenocarcinoma (LUAD) and identify vital lipid metabolism-related genes (LMRGs) that contribute to immunotherapy outcomes.
Materials and Methods
One thousand one hundred thirty LUAD patients were acquired utilizing public databases. Multiple algorithms were used to analyze the contribution of lipid metabolism in TIME. Importantly, cell lines, clinical samples (52 patients in surgery cohort and 36 in immunotherapy cohort), animal models, RNA sequencing (RNA-seq), experiments in protein and mRNA levels were conducted for identifying and validating key biomarker in LUAD immunotherapy.
Results
A prognostic signature comprising 33 LMRGs was developed and validated as an effective predictor of prognosis and TIME, with a C-index of 0.766 (95% confidence interval, 0.729 to 0.804). Additionally, we identified acyl-CoA synthetase long-chain family member 3 (ACSL3) as a potential biomarker for immunotherapy prognosis. The expression of ACSL3 was verified in 88 clinical tissues from LUAD patients, which indicated that elevated ACSL3 expression was correlated with worse progression-free survival (p < 0.001) and overall survival (p=0.008). Subsequent experiments revealed that knockdown of ACSL3 in vivo enhanced the efficacy of immunotherapy, potentially through increasing interferon-α secretion, as indicated by bulk RNA-seq and enzyme-linked immunosorbent assay analysis, thereby promoting the infiltration of antitumor immune cells.
Conclusion
The study established a model that accurately predicts immunotherapy response, prognosis, and TIME dynamics in LUAD patients. Notably, the pivotal role of ACSL3 in driving tumor progression and immune evasion was uncovered, offering novel insights into the optimization of immunotherapy strategies for LUAD.

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Pemetrexed Maintenance versus Observation in Patients with Advanced Urothelial Carcinoma Who Completed First-Line Platinum-Based Chemotherapy without Disease Progression (PREMIER, KCSG GU16-05): Inkeun Park, Shinkyo Yoon, Ilhwan Kim, Kwonoh Park, Suee Lee, Bhumsuk Keam, Joo-Hwan Park, Jin Young Kim, Yoon Ji Choi, Byeong Seok Sohn, Jae Lyun Lee; Received October 16, 2024 Accepted December 26, 2024 Published online December 27, 2024; DOI: https://doi.org/10.4143/crt.2024.1003 [Epub ahead of print]

Abstract PDF PubReader ePub: Purpose
Platinum-based chemotherapy is the standard treatment for advanced urothelial carcinoma (aUC). Switch maintenance therapy after first-line (1L) treatment may delay disease progression. This study evaluated pemetrexed as switch maintenance therapy versus observation in aUC patients without disease progression after initial chemotherapy.
Materials and Methods
Eligible aUC patients who did not progress after 4-6 cycles of cisplatin or carboplatin-based chemotherapy were randomized 1:1 to receive maintenance pemetrexed (500 mg/m² intravenously every 3 weeks, up to 16 cycles) or observation. The primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS), response rate, and safety.
Results
The trial was closed early due to slow accrual after avelumab approval. From October 2016 to December 2022, 97 patients were randomized to pemetrexed (n=49) or observation (n=48). The median age was 69 years (range, 43 to 90) and 66 (range, 33 to 82), respectively, with 63% and 73% of patients being male, respectively. The median PFS was 6.0 months (95% confidence interval [CI], 3.4 to 8.5) with pemetrexed versus 2.3 months (95% CI, 1.8 to 2.7) with observation (p=0.044; hazard ratio [HR], 0.64; 95% CI, 0.41 to 0.99). The median OS was 18.1 months (95% CI, 6.9 to 29.4) for pemetrexed and 17.9 months (95% CI, 16.1 to 19.7) for observation (p=0.913; HR, 1.03; 95% CI, 0.61 to 1.73). Common adverse events in the pemetrexed group included anemia (30.6%), fatigue (18.4%), and neutropenia (12.2%), primarily grade 1 or 2.
Conclusion
The PREMIER trial showed that switch maintenance pemetrexed significantly prolonged PFS in aUC patients post-1L platinum-based chemotherapy, with a favorable safety profile. Further studies on combination maintenance therapies are warranted.

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The Era of Antibody Drug Conjugates in Lung Cancer: Trick or Threat?: Mariona Riudavets, David Planchard; Cancer Res Treat. 2025;57(2):293-311. Published online November 28, 2024; DOI: https://doi.org/10.4143/crt.2024.714

Abstract PDF PubReader ePub: Antibody drug conjugates (ADCs) are a novel class of therapeutics that structurally are composed by an antibody directed to a tumor epitope connected via a linker to a cytotoxic payload, and that have shown significant antitumor activity across a range of malignancies including lung cancer. In this article we review the pharmacology and design of ADCs, as well as we describe the results of different studies evaluating ADCs in lung cancer directed to several targets including HER2, HER3, TROP2, MET, CEACAM5 and DLL3.

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Effectiveness and Safety of Regorafenib and TAS-102 in Patients with Metastatic Colorectal Cancer: A Nationwide Population-Based Study in Taiwan: Ya-Wen Chang, Chun-Nan Kuo, Chia-Lun Chang, Jason C. Hsu, Yu Ko; Received April 16, 2024 Accepted November 16, 2024 Published online November 18, 2024; DOI: https://doi.org/10.4143/crt.2024.376 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub: Purpose
This study aimed to examine the real-world effectiveness and safety of regorafenib and trifluridine/tipiracil (TAS-102) in metastatic colorectal cancer (mCRC) patients in Taiwan.
Materials and Methods
Data were extracted from Taiwan’s National Health Insurance Research Database to evaluate the clinical outcomes of mCRC patients treated with either regorafenib or TAS-102 between 2016 and 2019. Overall survival (OS) was compared using Kaplan-Meier curves and Cox’s proportional hazard models, adjusting for age, sex, Quan-CCI score, liver metastases, number of metastatic sites, and the use of anti–epidermal growth factor receptor medications. Additionally, OS was compared between regorafenib monotherapy and TAS-102 monotherapy, excluding patients who had received both regorafenib and TAS-102.
Results
A total of 2,608 patients in the regorafenib group and 521 patients in the TAS-102 group were identified. The median OS was 6.5 months for regorafenib and 7.5 months for TAS-102, with a significant difference observed (p=0.001). The mean duration of treatment was similar for regorafenib and TAS-102 (108 days vs. 101 days) with no significant difference. The safety profiles of the two drugs were distinct; a higher proportion of patients in the regorafenib group had hypertension and hand-foot skin reaction while nausea and vomiting were more common in the TAS-102 group. In the subgroup analysis, patients receiving TAS-102 monotherapy showed significantly longer OS than those receiving regorafenib monotherapy.
Conclusion
The findings of this study indicated that TAS-102 had superior survival outcomes compared to regorafenib in mCRC patients. This study provides insights into the effectiveness and safety profiles of regorafenib and TAS-102 in Taiwan.

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Breast cancer

Combination Therapy of Pyrotinib and Metronomic Vinorelbine in HER2+ Advanced Breast Cancer after Trastuzumab Failure (PROVE): A Prospective Phase 2 Study: Chunfang Hao, Xu Wang, Yehui Shi, Zhongsheng Tong, Shufen Li, Xiaodong Liu, Lan Zhang, Jie Zhang, Wenjing Meng, Li Zhang; Cancer Res Treat. 2025;57(2):434-442. Published online August 9, 2024; DOI: https://doi.org/10.4143/crt.2024.340

Abstract PDF PubReader ePub

Purpose
Approximately 50%-74% of patients with metastatic human epidermal growth factor receptor 2 (HER2)–positive breast cancer do not respond to trastuzumab, with 75% of treated patients experiencing disease progression within a year. The combination of pyrotinib and capecitabine has showed efficacy in these patients. This study evaluates the efficacy and safety of pyrotinib combined with metronomic vinorelbine for trastuzumab-pretreated HER2-positive advanced breast cancer patients.
Materials and Methods
In this phase 2 trial, patients aged 18-75 years with HER2-positive advanced breast cancer who had previously failed trastuzumab treatment were enrolled to receive pyrotinib 400 mg daily in combination with vinorelbine 40mg thrice weekly. The primary endpoint was progression-free survival (PFS), while secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety.
Results
From October 21, 2019, to January 21, 2022, 36 patients were enrolled and received at least one dose of study treatment. At the cutoff date, 20 experienced disease progression or death. With a median follow-up duration of 35 months, the median PFS was 13.5 months (95% confidence interval [CI], 8.3 to 18.5). With all patients evaluated, an ORR of 38.9% (95% CI, 23.1 to 56.5) and a DCR of 83.3% (95% CI, 67.2 to 93.6) were achieved. The median OS was not reached. Grade 3 adverse events (AEs) were observed in 17 patients, with diarrhea being the most common (27.8%), followed by vomiting (8.3%) and stomachache (5.6%). There were no grade 4/5 AEs.
Conclusion
Pyrotinib combined with metronomic vinorelbine showed promising efficacy and an acceptable safety profile in HER2-positive advanced breast cancer patients after trastuzumab failure.

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Adjuvant Metronomic Chemotherapy After Surgery in pT1-T2 N0 M0 HER2-Positive and ER/PR-Positive Breast Cancer Plus Targeted Therapy, Anti-Hormonal Therapy, and Radiotherapy, with or Without Immunotherapy: A New Operational Proposal
Luca Roncati
Cancers.2025; 17(8): 1323. CrossRef

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Gastrointestinal cancer

Fecal Microbial Dysbiosis Is Associated with Colorectal Cancer Risk in a Korean Population: Jeongseon Kim, Madhawa Gunathilake, Hyun Yang Yeo, Jae Hwan Oh, Byung Chang Kim, Nayoung Han, Bun Kim, Hyojin Pyun, Mi Young Lim, Young-Do Nam, Hee Jin Chang; Cancer Res Treat. 2025;57(1):198-211. Published online July 26, 2024; DOI: https://doi.org/10.4143/crt.2024.382

Abstract PDF Supplementary Material PubReader ePub

Purpose
The association between the fecal microbiota and colorectal cancer (CRC) risk has been suggested in epidemiologic studies. However, data from large-scale population-based studies are lacking.
Materials and Methods
In this case-control study, we recruited 283 CRC patients from the Center for Colorectal Cancer, National Cancer Center Hospital, Korea to perform 16S rRNA gene sequencing of fecal samples. A total of 283 age- and sex-matched healthy participants were selected from 890 cohort of healthy Koreans that are publicly available (PRJEB33905). The microbial dysbiosis index (MDI) was calculated based on the differentially abundant species. The association between MDI and CRC risk was observed using conditional logistic regression. Sparse Canonical Correlation Analysis was performed to integrate species data with microbial pathways obtained by PICRUSt2.
Results
There is a significant divergence of the microbial composition between CRC patients and controls (permutational multivariate analysis of variance p=0.001). Those who were in third tertile of the MDI showed a significantly increased risk of CRC in the total population (odds ratio [OR], 6.93; 95% confidence interval [CI], 3.98 to 12.06; p-trend < 0.001) compared to those in the lowest tertile. Similar results were found for men (OR, 6.28; 95% CI, 3.04 to 12.98; p-trend < 0.001) and women (OR, 7.39; 95% CI, 3.10 to 17.63; p-trend < 0.001). Bacteroides coprocola and Bacteroides plebeius species and 12 metabolic pathways were interrelated in healthy controls that explain 91% covariation across samples.
Conclusion
Dysbiosis in the fecal microbiota may be associated with an increased risk of CRC. Due to the potentially modifiable nature of the gut microbiota, our findings may have implications for CRC prevention among Koreans.

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Quantification of Naturally Occurring Prebiotics in Selected Foods
Arianna Natale, Federica Fiori, Federica Turati, Carlo La Vecchia, Maria Parpinel, Marta Rossi
Nutrients.2025; 17(4): 683. CrossRef

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Lung and Thoracic cancer

Differences in the Prognostic Impact between Single-Zone and Multi-Zone N2 Node Metastasis in Patients with Station-Based Multiple N2 Non–Small Cell Lung Cancer: Shia Kim, Geun Dong Lee, SeHoon Choi, Hyeong Ryul Kim, Yong-Hee Kim, Dong Kwan Kim, Seung-Il Park, Jae Kwang Yun; Cancer Res Treat. 2025;57(1):95-104. Published online July 22, 2024; DOI: https://doi.org/10.4143/crt.2024.120

Abstract PDF Supplementary Material PubReader ePub

Purpose
The International Association for the Study of Lung Cancer suggests further subdivision of pathologic N (pN) category in non–small-cell lung cancer (NSCLC) by incorporating the location and number of involved lymph node (LN) stations. We reclassified patients with the station-based N2b disease into single-zone and multi-zone N2b groups and compared survival outcomes between the groups.
Materials and Methods
This retrospective study included patients with pN2 NSCLC who underwent lobectomy from 2006 to 2019. The N2 disease was subdivided into four categories: single-station N2 without N1 (N2a1), single-station N2 with N1 (N2a2), multiple-station N2 with single zone involvement (single-zone N2b), and multiple-station N2 with multiple zone involvement (multi-zone N2b). LN zones included in the subdivision of N2 disease were upper mediastinal, lower mediastinal, aortopulmonary, and subcarinal.
Results
Among 996 eligible patients, 211 (21.2%), 394 (39.6%), and 391 (39.3%) were confirmed to have pN2a1, pN2a2, and pN2b disease, respectively. In multivariable analysis after adjustment for sex, age, pT category, and adjuvant chemotherapy, overall survival was significantly better with single-zone N2b disease (n=125, 12.6%) than with multi-zone N2b disease (n=266, 26.7%) (hazard ratio [HR], 0.67; 95% confidence interval [CI], 0.49 to 0.90; p=0.009) and was comparable to that of N2a2 disease (HR, 1.12; 95% CI, 0.83 to 1.49; p=0.46).
Conclusion
Prognosis of single-zone LN metastasis was better than that of multiple-zone LN metastasis in patients with N2b NSCLC. Along with the station-based N descriptors, zone-based descriptors might ensure optimal staging, enabling the most appropriate decision-making on adjuvant therapy for patients with pN2 NSCLC.

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Prediction of Lymph Node Metastasis in Non–Small Cell Lung Carcinoma Using Primary Tumor Somatic Mutation Data
Victor Lee, Nicholas S. Moore, Joshua Doyle, Daniel Hicks, Patrick Oh, Shari Bodofsky, Sajid Hossain, Abhijit A. Patel, Sanjay Aneja, Robert Homer, Henry S. Park
JCO Clinical Cancer Informatics.2025;[Epub] CrossRef

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Hematologic malignancy

Assessing the Efficacy of Bortezomib and Dexamethasone for Induction and Maintenance Therapy in Relapsed/Refractory Cutaneous T-Cell Lymphoma: A Phase II CISL1701/BIC Study: Yoon Seok Choi, Joonho Shim, Ka-Won Kang, Sang Eun Yoon, Jun Sik Hong, Sung Nam Lim, Ho-Young Yhim, Jung Hye Kwon, Gyeong-Won Lee, Deok-Hwan Yang, Sung Yong Oh, Ho-Jin Shin, Hyeon-Seok Eom, Dok Hyun Yoon, Hong Ghi Lee, Seong Hyun Jeong, Won Seog Kim, Seok Jin Kim; Cancer Res Treat. 2025;57(1):267-279. Published online July 16, 2024; DOI: https://doi.org/10.4143/crt.2024.479

Abstract PDF Supplementary Material PubReader ePub: Purpose
This multicenter, open-label, phase II trial evaluated the efficacy and safety of bortezomib combined with dexamethasone for the treatment of relapsed/refractory cutaneous T-cell lymphoma (CTCL) in previously treated patients across 14 institutions in South Korea.
Materials and Methods
Between September 2017 and July 2020, 29 patients with histologically confirmed CTCL received treatment, consisting of eight 4-week cycles of induction therapy followed by maintenance therapy, contingent upon response, for up to one year. The primary endpoint was the proportion of patients achieving an objective global response.
Results
Thirteen of the 29 patients (44.8%) achieved an objective global response, including two complete responses. The median progression-free survival (PFS) was 5.8 months, with responders showing a median PFS of 14.0 months. Treatment-emergent adverse events were generally mild, with a low incidence of peripheral neuropathy and hematologic toxicities. Despite the trend toward shorter PFS in patients with higher mutation burdens, genomic profiling before and after treatment showed no significant emergence of new mutations indicative of disease progression.
Conclusion
This study supports the use of bortezomib and dexamethasone as a viable and safe treatment option for previously treated CTCL, demonstrating substantial efficacy and manageability in adverse effects. Further research with a larger cohort is suggested to validate these findings and explore the prognostic value of mutation profiles.

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Breast cancer

A Single-Arm Phase II Clinical Trial of Fulvestrant Combined with Neoadjuvant Chemotherapy of ER+/HER2– Locally Advanced Breast Cancer: Integrated Analysis of ¹⁸F-FES PET-CT and Metabolites with Treatment Response: Qing Shao, Ningning Zhang, Xianjun Pan, Wenqi Zhou, Yali Wang, Xiaoliang Chen, Jing Wu, Xiaohua Zeng; Cancer Res Treat. 2025;57(1):126-139. Published online July 9, 2024; DOI: https://doi.org/10.4143/crt.2023.1251

Abstract PDF Supplementary Material PubReader ePub: Purpose
This Phase II trial was objected to evaluate the efficacy and safety of adding fulvestrant to neoadjuvant chemotherapy in patients with estrogen receptor (ER)+/human epidermal growth factor receptor 2 (HER2)– locally advanced breast cancer (LABC). Additionally, the study aimed to investigate the association of 16α-18F-fluoro-17β-fluoroestradiol (¹⁸F-FES) positron emission tomography (PET)–computed tomography (CT) and metabolites with efficacy.
Materials and Methods
Fulvestrant and EC-T regimen were given to ER+/HER2– LABC patients before surgery. At baseline, patients received ¹⁸F-FES PET-CT scan, and plasma samples were taken for liquid chromatography–mass spectrometry analysis. The primary endpoint was objective response rate (ORR). Secondary endpoints included total pathologic complete response (tpCR) and safety.
Results
Among the 36 patients enrolled, the ORR was 86.1%, the tpCR rate was 8.3%. The incidence of grade ≥ 3 treatment-emergent adverse events was 22%. The decrease in ER value in sensitive patients was larger than that in non-sensitive patients, as was Ki-67 (p < 0.05). The maximum standardized uptake value, mean standardized uptake values, total lesion ER expression of ¹⁸F-FES PET-CT in sensitive patients were significantly higher than those in non-sensitive patients (p < 0.05). Moreover, these parameters were significantly correlated with Miller and Payne grade and the change in ER expression before and after treatment (p < 0.05). Thirteen differential expressed metabolites were identified, which were markedly enriched in 19 metabolic pathways.
Conclusion
This regimen demonstrated acceptable toxicity and encouraging antitumor efficacy. ¹⁸F-FES PET-CT might serve as a tool to predict the effectiveness of this therapy. Altered metabolites or metabolic pathways might be associated with treatment response.

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154 Download

Dural Metastasis in Breast Cancer: MRI-Based Morphological Subtypes and Their Clinical Implications: Sung Jun Ahn, Bio Joo, Mina Park, Hun Ho Park, Sang Hyun Suh, Sung Gwe Ahn, Jihwan Yoo; Cancer Res Treat. 2024;56(4):1105-1112. Published online March 19, 2024; DOI: https://doi.org/10.4143/crt.2024.138

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study aimed to investigate the clinical factors associated with breast cancer (BRCA) dural metastases (DMs), their impact on prognosis compared to brain parenchymal metastases (BPMs) alone, and differences between DM subtypes, aiming to inform clinical decisions.
Materials and Methods
We retrospectively analyzed 119 patients with BRCA with brain metastasis, including 91 patients with BPM alone and 28 patients with DM. Univariate and multivariate analyses were performed to compare the clinical characteristics between the two groups and within subtypes of DM. Overall survival after DM (OSDM) and the interval from DM to leptomeningeal carcinomatosis (LMC) were compared using Kaplan-Meier analysis.
Results
DM was notably linked with extracranial metastasis, luminal-like BRCA subtype (p=0.033), and skull metastases (p < 0.001). Multiple logistic regression revealed a strong association of DM with extracranial and skull metastases, but not with subtype or hormone receptor status. Patients with DM did not show survival differences compared with patients with BPM alone. In the subgroup analysis, nodular-type DM correlated with human epidermal growth factor receptor 2 status (p=0.044), whereas diffuse-type DM was significantly associated with a higher prevalence of the luminal-like subtype (p=0.048) and the presence of skull metastasis (p=0.002). Patients with diffuse DM did not exhibit a significant difference in OSDM but had a notably shorter interval from DM to LMC compared to those with nodular DM (p=0.049).
Conclusion
While the impact of DM on the overall prognosis of patients with BRCA is minimal, our findings underscore distinct characteristics and prognostic outcomes within DM subgroups.

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Small-cell neuroendocrine carcinoma of the cervix with leptomeningeal spread: A rare coincidence report and literature review
Mohammed A. Azab, Oday Atallah, Nour El-Gohary, Ahmed Hazim, Hamed Abdelma’aboud Mostafa
Surgical Neurology International.2024; 15: 310. CrossRef
Left homonymous hemianopia as an atypical manifestation of isolated pachymeningeal metastasis secondary to breast cancer: Case report and review of the literature
Aziz Ahizoune, Moad Belouad, Houda Alloussi, Mohamed Allaoui, Mohamed Hamid, Ahmed Bourazza
Radiology Case Reports.2024; 19(11): 5459. CrossRef

2,007 View
87 Download
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2 Crossref

Endocrine cancer

Combination of Dabrafenib and Trametinib in Patients with Metastatic BRAF^V600E-Mutated Thyroid Cancer: Youngkyung Jeon, Sehhoon Park, Se-Hoon Lee, Tae Hyuk Kim, Sun Wook Kim, Myung-Ju Ahn, Hyun Ae Jung, Jae Hoon Chung; Cancer Res Treat. 2024;56(4):1270-1276. Published online March 6, 2024; DOI: https://doi.org/10.4143/crt.2023.1278

Abstract PDF Supplementary Material PubReader ePub

Purpose
BRAF mutations are detected in 30%-80% of papillary thyroid cancer (PTC) cases. DaBRAFenib and trametinib showed promising antitumor activity in patients with BRAF^V600E-mutated metastatic melanoma and non–small cell lung cancer. This study aimed to evaluate the efficacy and safety of daBRAFenib and trametinib in patients with metastatic BRAF^V600E-mutated thyroid cancer.
Materials and Methods
This was a retrospective study to evaluate the efficacy of daBRAFenib and trametinib in patients with metastatic BRAF^V600E-mutated PTC. The patients received daBRAFenib 150 mg twice daily and trametinib 2 mg once daily at the Samsung Medical Center. This study evaluated the progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR) overall survival (OS), and safety of daBRAFenib and trametinib.
Results
Between December 2019 and January 2022, 27 PTC patients including eight patients with poorly differentiated or anaplastic transformation, received daBRAFenib and trametinib. The median age was 73.0 years, and the median follow-up period was 19.8 months. The majority (81.5%) had undergone thyroidectomy, while 8 patients had received prior systemic treatments. ORR was 73.1%, with 19 partial responses, and DCR was 92.3%. Median PFS was 21.7 months, and median OS was 21.7 months. Treatment-related adverse events included generalized weakness (29.6%), fever (25.9%), and gastrointestinal problems (22.2%). Dose reduction due to adverse events was required in 81.5% of the patients.
Conclusion
DaBRAFenib and trametinib demonstrated a high ORR with promising PFS; however, most patients with BRAF^V600E-mutated metastatic PTC required a dose reduction.

Citations

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A comprehensive review of RAF kinase: advances in inhibition strategies for drug development
Dilay Kahvecioglu
Journal of Molecular Structure.2025; 1337: 142206. CrossRef
Development of a coagulation‑related gene model for prognostication, immune response and treatment prediction in lung adenocarcinoma
Jia Li, Xuedi Gao, Lin Lv, Yubin Huang, Houlu Zhang, Xiaoming Sun, Liangming Zhu
Oncology Letters.2025; 29(6): 1. CrossRef
Systemic Therapeutic Options in Radioiodine-Refractory Differentiated Thyroid Cancer: Current Indications and Optimal Timing
Tamara Díaz Vico, Brezo Martínez-Amores Martínez, Luka Mihic Góngora, Paula Jiménez-Fonseca, Paloma Peinado Martín, Irene Grao Torrente, Alejandro García Muñoz-Nájar, Manuel Durán-Poveda
Cancers.2025; 17(11): 1800. CrossRef
Thyroid Cancer: Epidemiology, Classification, Risk Factors, Diagnostic and Prognostic Markers, and Current Treatment Strategies
Alicja Forma, Karolina Kłodnicka, Weronika Pająk, Jolanta Flieger, Barbara Teresińska, Jacek Januszewski, Jacek Baj
International Journal of Molecular Sciences.2025; 26(11): 5173. CrossRef
Korean Thyroid Association Guidelines on the Management of Differentiated Thyroid Cancers; Part III. Management of Advanced Differentiated Thyroid Cancers - Chapter 4. Systemic Therapy for Progressive Radioiodine-Refractory Differentiated Thyroid Cancer 2
Dong Yeob Shin, Ho-Cheol Kang, Sun Wook Kim, Dong Gyu Na, Young Joo Park, Young Shin Song, Eun Kyung Lee, Dong-Jun Lim, Yun Jae Chung, Won Gu Kim
International Journal of Thyroidology.2024; 17(1): 168. CrossRef
Antineoplastic Effect of ALK Inhibitor Crizotinib in Primary Human Anaplastic Thyroid Cancer Cells with STRN–ALK Fusion In Vitro
Silvia Martina Ferrari, Francesca Ragusa, Giusy Elia, Valeria Mazzi, Eugenia Balestri, Chiara Botrini, Licia Rugani, Armando Patrizio, Simona Piaggi, Concettina La Motta, Salvatore Ulisse, Camilla Virili, Alessandro Antonelli, Poupak Fallahi
International Journal of Molecular Sciences.2024; 25(12): 6734. CrossRef
The Long Journey towards Personalized Targeted Therapy in Poorly Differentiated Thyroid Carcinoma (PDTC): A Case Report and Systematic Review
Odysseas Violetis, Panagiota Konstantakou, Ariadni Spyroglou, Antonios Xydakis, Panagiotis B. Kekis, Sofia Tseleni, Denise Kolomodi, Manousos Konstadoulakis, George Mastorakos, Maria Theochari, Javier Aller, Krystallenia I. Alexandraki
Journal of Personalized Medicine.2024; 14(6): 654. CrossRef
Treatment of Unresectable BRAF V600E, TERT-Mutated Differentiated Papillary Thyroid Cancer With Dabrafenib and Trametinib
Neha Bapat, Tatiana Ferraro, Layal Esper, Arjun S Joshi, Faysal Haroun, Chelsey K Baldwin
JCEM Case Reports.2024;[Epub] CrossRef
Trametinib

Reactions Weekly.2024; 2035(1): 467. CrossRef

5,048 View
457 Download
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9 Crossref

Head and Neck cancer

Metronomic S-1 Adjuvant Chemotherapy Improves Survival in Patients with Locoregionally Advanced Nasopharyngeal Carcinoma: Yi-Feng Yu, Peng Wu, Rui Zhuo, San-Gang Wu; Cancer Res Treat. 2024;56(4):1058-1067. Published online February 19, 2024; DOI: https://doi.org/10.4143/crt.2023.1343

Abstract PDF PubReader ePub

Purpose
This study aimed to investigate the efficacy and safety of using metronomic S-1 adjuvant chemotherapy in locoregionally advanced nasopharyngeal carcinoma (LANPC).
Materials and Methods
We retrospectively collected data on patients diagnosed with LANPC between January 2016 and December 2021. All patients were treated with induction chemotherapy and concurrent chemoradiotherapy with or without metronomic chemotherapy (MC). Toxicities during MC were recorded. The chi-square test, Kaplan-Meier methods, propensity score matching (PSM), and Cox proportional hazards model were used for statistical analyses.
Results
A total of 474 patients were identified, including 64 (13.5%) and 410 (83.5%) patients with or without receiving MC, respectively. Patients who received metronomic S-1 had significantly better 3-year locoregional recurrence-free survival (LRFS) (100% vs. 90.9%, p=0.038), distant metastasis-free survival (DMFS) (98.5% vs. 84.1%, p=0.002), disease-free survival (DFS) (98.4% vs. 77.5%, p < 0.001), and overall survival (OS) (98.0% vs. 87.7%, p=0.008) compared to those without metronomic S-1. The multivariate prognostic analysis revealed that metronomic S-1 was identified as an independent prognostic factor associated with better DMFS (hazard ratio [HR], 0.074; p=0.010), DFS (HR, 0.103; p=0.002) and OS (HR, 0.127; p=0.042), but not in LRFS (p=0.071). Similar results were found using PSM. Common adverse events observed in the metronomic S-1 group included leukopenia, neutropenia, increased total bilirubin, anorexia, rash/desquamation, and hyperpigmentation. All patients with adverse events were grade 1-2.
Conclusion
It is worth conducting a randomized controlled trial to assess the effect of metronomic S-1 on survival outcomes and toxicities of LANPC.

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Reply to Commentary on “Metronomic S-1 Adjuvant Chemotherapy Improves Survival in Patients with Locoregionally Advanced Nasopharyngeal Carcinoma”
San-Gang Wu
Cancer Research and Treatment.2025; 57(1): 291. CrossRef
Commentary on “Metronomic S-1 Adjuvant Chemotherapy Improves Survival in Patients with Locoregionally Advanced Nasopharyngeal Carcinoma”
Erkan Topkan, Efsun Somay, Nilufer Kılıc Durankus, Ugur Selek
Cancer Research and Treatment.2025; 57(1): 289. CrossRef
Short-term versus long-term metronomic adjuvant chemotherapy in locally advanced nasopharyngeal carcinoma: A propensity score-matched real-world study
Shuhui Dong, Weixin Bei, Lanfeng Lin, Yaofei Jiang, Nian Lu, Guoying Liu, Yanqun Xiang, Weixiong Xia
Oral Oncology.2024; 156: 106908. CrossRef

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Breast cancer

Trastuzumab Biosimilar (HLX02), Pertuzumab Plus Chemotherapy in Patients with HER2-Positive Metastatic Breast Cancer after Progression of Trastuzumab: A Prospective, Phase II Study: Ruyan Zhang, Xiaoran Liu, Guohong Song, Yan Zhang, Huiping Li; Cancer Res Treat. 2024;56(3):795-801. Published online December 20, 2023; DOI: https://doi.org/10.4143/crt.2023.1151

Abstract PDF PubReader ePub: Purpose
This study aims to evaluate the efficacy and safety of trastuzumab biosimilar (HLX02) in combination with pertuzumab and chemotherapy in patients with human epidermal growth factor receptor 2 (HER2)–positive metastatic breast cancer (MBC) after progression of trastuzumab.
Materials and Methods
In this prospective, single-arm, phase II study, patients with HER2-positive MBC after progression of trastuzumab received pertuzuamb, HLX02, and chemotherapy in Beijing Cancer Hospital from March 2020 to December 2022. The primary endpoint was progression-free survival (PFS), and secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. The study was registered with ClinicalTrials.gov (NCT05188495).
Results
A total of 45 patients were included in this study. Twelve patients (26.7%) were treated in second-line and 33 patients (73.3%) were in third-line and later setting. Eighty percent and 15.5% patients had previously received pyrotinib/lapatinib and T-DM1, respectively. With a median follow-up of 24.4 months (range, 1.2 to 43.9 months), the median PFS was 7.6 months (95% confidence interval, 4.3 to 10.9), OS was not reached, the ORR was 31.1%, and DCR was 91.1%. The treatment was well tolerated.
Conclusion
The combination of trastuzumab biosimilar HLX02, pertuzumab, and chemotherapy exhibited promising efficacy and a favorable safety profile as second- and beyond-line treatment in HER2-positive MBC.

4,811 View
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Gastrointestinal cancer

The Clinical Efficacy of Colorectal Cancer Patients with Pulmonary Oligometastases by Sterotactic Body Ablative Radiotherapy: A Meta-Analysis: Jae-Uk Jeong, Chai Hong Rim, Gyu Sang Yoo, Won Kyung Cho, Eui Kyu Chie, Yong Chan Ahn, Jong Hoon Lee, on behalf of Korean Oligometastasis Working Group, Korean Cancer Association; Cancer Res Treat. 2024;56(3):809-824. Published online December 14, 2023; DOI: https://doi.org/10.4143/crt.2023.920

Abstract PDF Supplementary Material PubReader ePub

Purpose
There is increasing interest in the efficacy of stereotactic ablative radiotherapy (SABR) for treating colorectal cancer (CRC) patients with oligometastases (OM), recently. The purpose of this meta-analysis was to evaluate local control (LC), progression-free survival (PFS), and overall survival (OS) of CRC patients with pulmonary OM treated with SABR and toxicities.
Materials and Methods
Studies that reported SABR for CRC patients with pulmonary OM were searched from MEDLINE and Embase. Treatment outcomes including LC, PFS, OS, and toxicities of grade 3 or higher were assessed.
Results
A total of 19 studies with 1,668 patients were chosen for this meta-analysis. Pooled 1-, 2-, and 3-year LC rates were 83.1%, 69.3%, and 63.9%, respectively. PFS rates were 44.8%, 26.5%, and 21.5% at 1, 2, and 3 years, respectively. OS rates at 1-, 2-, and 3-year were 87.5%, 69.9%, and 60.5%, respectively. The toxicity rate of grade 3 or higher was 3.6%. The effect of dose escalation was meta-analyzed using available studies.
Conclusion
Application of SABR to CRC patients with pulmonary OM achieved modest local control with acceptable toxicity according to the present meta-analysis. Further studies establishing the clinical efficacy of SABR are guaranteed.

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Identifying Trends in Oncology Research through a Bibliographic Analysis of Cancer Research and Treatment
Choong-kun Lee, Jeong Min Choo, Yong Chan Ahn, Jin Kim, Sun Young Rha, Chai Hong Rim
Cancer Research and Treatment.2025; 57(1): 11. CrossRef

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1 Crossref

Breast cancer

PD-L1 (SP142) Expression in Primary and Recurrent/Metastatic Triple-Negative Breast Cancers and Its Clinicopathological Significance: Eun Kyung Han, Ji Won Woo, Koung Jin Suh, Se Hyun Kim, Jee Hyun Kim, So Yeon Park; Cancer Res Treat. 2024;56(2):557-566. Published online December 12, 2023; DOI: https://doi.org/10.4143/crt.2023.1025

Abstract PDF PubReader ePub

Purpose
The programmed death-ligand 1 (PD-L1) SP142 assay identifies patients with triple-negative breast cancer (TNBC) who are most likely to respond to the anti–PD-L1 agent atezolizumab. We aimed to compare PD-L1 (SP142) expression between primary and recurrent/metastatic TNBCs and elucidate the clinicopathological features associated with its expression.
Materials and Methods
Primary and recurrent/metastatic TNBCs tested with PD-L1 (SP142) were collected, and clinicopathological information of these cases was obtained through a review of slides and medical records.
Results
PD-L1 (SP142) positivity was observed in 50.9% (144/283) of primary tumors and 37.8% (31/82) of recurrent/metastatic TNBCs with a significant difference. Recurrent or metastatic sites were associated with PD-L1 positivity, with high PD-L1 positivity in the lung, breast, and soft tissues, and low positivity in the bone, skin, liver, and brain. When comparing PD-L1 expression between primary and matched recurrent/metastatic TNBCs using 55 paired samples, 20 cases (36.4%) showed discordance; 10 cases revealed positive conversion, and another 10 cases revealed negative conversion during metastatic progression. In primary TNBCs, PD-L1 expression was associated with a higher histologic grade, lower T category, pushing border, and higher tumor-infiltrating lymphocyte infiltration. In survival analyses, PD-L1 positivity, especially high positivity, was found to be associated with favorable prognosis of patients.
Conclusion
PD-L1 (SP142) expression was lower in recurrent/metastatic TNBCs, and substantial cases showed discordance in its expression between primary and recurrent/metastatic sites, suggesting that multiple sites may need to be tested for PD-L1 (SP142) when considering atezolizumab therapy. PD-L1 (SP142)–positive TNBCs seems to be associated with favorable clinical outcomes.

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Discrepancy of PD1/ PD-L1 status between primary and metastatic triple negative breast cancer in diagnostic biopsies
Manar Moustafa, Basma Hamed Ibrahim
Revista de Senología y Patología Mamaria.2025; 38(3): 100680. CrossRef
Solamargine inhibits gastric cancer progression via inactivation of STAT3/PD‑L1 signaling
Xiongxiang Liu, Lin Song, Wen Liu, Bin Liu, Lang Liu, Yao Su
Molecular Medicine Reports.2024;[Epub] CrossRef
Prevalence of Programmed Death-Ligand 1 Positivity Using SP142 in Patients With Advanced Stage Triple-Negative Breast Cancer in Malaysia: A Cross-Sectional Study
Pathmanathan Rajadurai, Ning Yi Yap, Seow Fan Chiew, Reena Rahayu Md Zin, Suria Hayati Md Pauzi, Aniqah Shamimi Binti Jaafar, Azyani Yahaya, Lai Meng Looi
Journal of Breast Cancer.2024; 27(6): 362. CrossRef

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Lung and Thoracic cancer

Development of the Korean Association for Lung Cancer Clinical Practice Guidelines: Recommendations on Radial Probe Endobronchial Ultrasound for Diagnosing Lung Cancer - An Updated Meta-Analysis: Soo Han Kim, Hyun Sung Chung, Jinmi Kim, Mi-Hyun Kim, Min Ki Lee, Insu Kim, Jung Seop Eom; Cancer Res Treat. 2024;56(2):464-483. Published online November 29, 2023; DOI: https://doi.org/10.4143/crt.2023.749

Abstract PDF Supplementary Material PubReader ePub

Purpose
Radial probe endobronchial ultrasound (RP-EBUS) accurately locates peripheral lung lesions (PLLs) during transbronchial biopsy (TBB). We performed an updated meta-analysis of the diagnostic yield of TBB for PLLs using RP-EBUS to generate recommendations for the development of the Korean Association of Lung Cancer guidelines.
Materials and Methods
We systematically searched MEDLINE and EMBASE (from January 2013 to December 2022), and performed a meta-analysis using R software. The diagnostic yield was evaluated by dividing the number of successful diagnoses by the total lesion number. Subgroup analysis was performed to identify related factors.
Results
Forty-one studies with a total of 13,133 PLLs were included. The pooled diagnostic yield of RP-EBUS was 0.72 (95% confidence interval [CI], 0.70 to 0.75). Significant heterogeneity was observed among studies (χ²=292.38, p < 0.01, I²=86.4%). In a subgroup analysis, there was a significant difference in diagnostic yield based on RP-EBUS findings (within, adjacent to, invisible), with a risk ratio of 1.45 (95% CI, 1.23 to 1.72) between within and adjacent to, 4.20 (95% CI, 1.89 to 9.32) between within and invisible, and 2.59 (95% CI, 1.32 to 5.01) between adjacent to and invisible. There was a significant difference in diagnostic yield based on lesion size, histologic diagnosis, computed tomography (CT) bronchus sign, lesion character, and location from the hilum. The overall complication rate of TBB with RP-EBUS was 6.8% (bleeding, 4.5%; pneumothorax, 1.4%).
Conclusion
Our study showed that TBB with RP-EBUS is an accurate diagnostic tool for PLLs with good safety profiles, especially for PLLs with within orientation on RP-EBUS or positive CT bronchus sign.

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Can intraoperative improvement of radial endobronchial ultrasound imaging enhance the diagnostic yield in peripheral pulmonary lesions?
Kazuki Nishida, Takayasu Ito, Shingo Iwano, Shotaro Okachi, Shota Nakamura, Basile Chrétien, Toyofumi Fengshi Chen-Yoshikawa, Makoto Ishii
BMC Pulmonary Medicine.2025;[Epub] CrossRef

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166 Download
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General

Radiation Oncologists’ Perspectives on Oligometastatic Disease: A Korean Survey Study: Chai Hong Rim, Won Kyung Cho, Jong Hoon Lee, Young Seok Kim, Yang-Gun Suh, Kyung Hwan Kim, Ah Ram Chang, Eui Kyu Chie, Yong Chan Ahn, on behalf of the Oligometastasis Working Group, Korean Cancer Association; Cancer Res Treat. 2024;56(2):414-421. Published online November 22, 2023; DOI: https://doi.org/10.4143/crt.2023.876

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Purpose
Perspectives of radiation oncologists on oligometastatic disease was investigated using multi-layered survey.
Materials and Methods
Online survey on the oligometastatic disease was distributed to the board-certified regular members of the Korean Society for Radiation Oncology. The questionnaire consisted of four domains: five questions on demographics; five on the definition of oligometastatic disease; four on the role of local therapy; and three on the oligometastatic disease classification, respectively.
Results
A total of 135 radiation oncologists participated in the survey. The median length of practice after board certification was 22.5 years (range, 1 to 44 years), and the vast majority (94.1%) answered affirmatively to the clinical experience in oligometastatic disease management. Nearly two-thirds of the respondents considered the number of involved organs as an independent factor in defining oligometastasis. Most frequently perceived upper limit on the numerical definition of oligometastasis was 5 (64.2%), followed by 3 (26.0%), respectively. Peritoneal and brain metastasis were nominated as the sites to be excluded from oligometastastic disease by 56.3% and 12.6% of the participants, respectively. Vast majority (82.1%) agreed on the role of local treatment in the management of oligometastatic disease. Majority (72%) of the participants acknowledged the European Society for Radiotherapy and Oncology (ESTRO)–European Organisation for Research and Treatment of Cancer (EORTC) classification of oligometastatic disease, however, only 43.3% answered that they applied this classification in their clinical practice. Underlying reasons against the clinical use were ‘too complicated’ (66.0%), followed by ‘insufficient supporting evidence’ (30.0%), respectively.
Conclusion
While most radiation oncologists supported the role of local therapy in oligometastatic disease, there were several inconsistencies in defining and categorizing oligometastatic disease. Continued education and training on oligometastatic disease would be also required to build consensus among participating caregivers.

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Efficacy Analysis of Hypofractionated Radiotherapy for Oligometastatic Tumors: A Retrospective Study
Qian Sun, Hanqing Zhao, Xianwen Zhang, Suli Zhang, Zelai He, Gengming Wang, Hao Jiang, Aili Xuan, Xianming Li
Technology in Cancer Research & Treatment.2025;[Epub] CrossRef
‘Perspectives of pulmonologists and thoracic surgeons on Oligometastatic disease: curability, treatment approaches, and disease trajectory’
Damla Azaklı, Inanc Yazici, Aysegul Erinc, Celal Satici
Future Oncology.2025; : 1. CrossRef
Expert consensus on radiotherapy for oligometastatic esophageal cancer (2025 edition)
Zhiguo Zhou, Xiaoyan Lv, Jun Wang, Zhouguang Hui, Qingsong Pang
Radiation Medicine and Protection.2025;[Epub] CrossRef
A new proposal of simplified classification of non-small cell lung cancer oligometastases for easy applicability through systematic literature analysis and meta-analysis validation
Hanseung Kang, Woohyeon Do, Yong Chan Ahn, Eui Kyu Chie, Chai Hong Rim
European Journal of Cancer.2024; 212: 115043. CrossRef

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Lung and Thoracic cancer

Genomic Landscape of Pulmonary Sarcomatoid Carcinoma: Hyun Jung Kwon, Sejoon Lee, Yeon Bi Han, Jeonghyo Lee, Soohyeon Kwon, Hyojin Kim, Jin-Haeng Chung; Cancer Res Treat. 2024;56(2):442-454. Published online November 14, 2023; DOI: https://doi.org/10.4143/crt.2023.764

Abstract PDF Supplementary Material PubReader ePub

Purpose
Pulmonary sarcomatoid carcinoma (PSC) is a rare aggressive subtype of non–small cell lung cancer (NSCLC) with limited therapeutic strategies. We attempted to elucidate the evolutionary trajectories of PSC using multiregional and longitudinal tumor samples.
Materials and Methods
A total of 31 patients were enrolled in this study and 11 longitudinal samples were available from them. Using whole exome sequencing data, we analyzed the mutational signatures in both carcinomatous and sarcomatous areas in primary tumors of the 31 patients and longitudinal samples obtained from 11 patients. Furthermore, digital droplet polymerase chain reaction (ddPCR), and programmed death-ligand 1 (PD-L1) immunohistochemistry using the Ventana SP263 assay were performed.
Results
TP53 was identified as the most frequently altered gene in the primary (74%) and metastatic (73%) samples. MET exon 14 skipping mutations, confirmed by ddPCR, and TP53 mutations were mutually exclusive; whereas, MET exon 14 skipping mutations frequently co-occurred with MDM2 amplification. Metastatic tumors showed dissimilar genetic profiles from either primary component. During metastasis, the signatures of APOBEC decreased in metastatic lesions compared with that in primary lesions. PSC showed higher MET and KEAP1 mutations and stronger PD-L1 protein expression compared with that recorded in other NSCLCs.
Conclusion
Decreased APOBEC signatures and subclonal diversity were detected during malignant progression in PSC. Frequent MET mutations and strong PD-L1 expression distinguished PSC from other NSCLCs. The aggressiveness and therapeutic difficulties of PSC were possibly attributable to profound intratumoral and intertumoral genetic diversity. Next-generation sequencing could suggest the appropriate treatment strategy for PSC.

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Pulmonary pleomorphic carcinoma associated with cystic airspace and recurrent spontaneous pneumothorax: A case report
Qiangsheng Li, Jing Zhang, Youjie Gong, Xudong Wan, Song Zhang, Zhongwang Li, Jun Liu
Oncology Letters.2025; 30(1): 1. CrossRef
Combination of epirubicin and cyclophosphamide for the treatment of advanced pulmonary sarcomatoid carcinoma: A case report and literature review
Ruoyu Deng, Jialing Lv, Fang Wang, Yanqiong Chen, Junfeng Wang, Lin Wang, Lixia Mu, Zhijun Zhang, Wen Zhang, Chao Zhang
Journal of Cancer Research and Therapeutics.2025; 21(2): 512. CrossRef
Challenges in the Recognition and Management of Metastatic Sarcomatoid Carcinoma Masquerading As Post-traumatic Hematoma
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PD-L1 Expression and Its Modulating Factors in Anaplastic Thyroid Carcinoma
Shipra Agarwal, Chan Kwon Jung, Pranitha Gaddam, Mitsuyoshi Hirokawa, Takuya Higashiyama, Jen-Fan Hang, Wei-An Lai, Somboon Keelawat, Zhiyan Liu, Hee Young Na, So Yeon Park, Junya Fukuoka, Shinya Satoh, Zhanna Mussazhanova, Masahiro Nakashima, Kennichi Ka
American Journal of Surgical Pathology.2024; 48(10): 1233. CrossRef

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Gastrointestinal cancer

Gemcitabine Inhibits the Progression of Pancreatic Cancer by Restraining the WTAP/MYC Chain in an m6A-Dependent Manner: Pei Cao, Weigang Zhang, Junyi Qiu, Zuxiong Tang, Xiaofeng Xue, Tingting Feng; Cancer Res Treat. 2024;56(1):259-271. Published online August 16, 2023; DOI: https://doi.org/10.4143/crt.2022.1600

Abstract PDF Supplementary Material PubReader ePub

Purpose
Pancreatic cancer (PC) is a common malignant tumor of the digestive system, and its 5-year survival rate is only 4%. N6-methyladenosine (m6A) RNA methylation is the most common post-transcriptional modification and dynamically regulates cancer development, while its role in PC treatment remains unclear.
Materials and Methods
We treated PC cells with gemcitabine and quantified the overall m6A level with m6A methylation quantification. Real-time quantitative reverse transcription polymerase chain reaction and Western blot analyses were used to detect expression changes of m6A regulators. We verified the m6A modification on the target genes through m6A-immunoprecipitation (IP), and further in vivo experiments and immunofluorescence (IF) assays were applied to verify regulation of gemcitabine on Wilms’ tumor 1–associated protein (WTAP) and MYC.
Results
Gemcitabine inhibited the proliferation and migration of PC cells and reduced the overall level of m6A modification. Additionally, the expression of the “writer” WTAP was significantly downregulated after gemcitabine treatment. We knocked down WTAP in cells and found target gene MYC expression was significantly downregulated, m6A-IP also confirmed the m6A modification on MYC. Our experiments showed that m6A-MYC may be recognized by the “reader” IGF2BP1. In vivo experiments revealed gemcitabine inhibited the tumorigenic ability of PC cells. IF analysis also showed that gemcitabine inhibited the expression of WTAP and MYC, which displayed a significant trend of co-expression.
Conclusion
Our study confirmed that gemcitabine interferes with WTAP protein expression in PC, reduces m6A modification on MYC and RNA stability, thereby inhibiting the downstream pathway of MYC, and inhibits the progression of PC.

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Li Qiu, Shourong Wu, Lei Zhang, Wenfang Li, Debing Xiang, Vivi Kasim
Genes & Diseases.2025; 12(5): 101567. CrossRef
Long Non-Coding RNAs and RNA-Binding Proteins in Pancreatic Cancer Development and Progression
Pit Preckwinkel, Khursheed Ul Islam Mir, Florian W. Otto, Hend Elrewany, Andrea Sinz, Stefan Hüttelmaier, Nadine Bley, Tony Gutschner
Cancers.2025; 17(10): 1601. CrossRef
CALB2 facilitates macrophage M2 polarization to promote the growth and metastasis of pancreatic adenocarcinoma
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Shaoyang Zhang, Qinghui Fu, Zhipeng Xu, Mingjie Fu, Jianfeng Zhao, Wenqiao Yu
Hereditas.2025;[Epub] CrossRef
WTAP-mediated N6-methyladenosine modification promotes the inflammation, mitochondrial damage and ferroptosis of kidney tubular epithelial cells in acute kidney injury by regulating LMNB1 expression and activating NF-κB and JAK2/STAT3 pathways
Fan Huang, Yuchen Wang, XiaoLi Lv, Chenda Huang
Journal of Bioenergetics and Biomembranes.2024; 56(3): 285. CrossRef

3,769 View
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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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The genetic architecture of bone metastases: unveiling the role of epigenetic and genetic modifications in drug resistance
Ahmad Dawalibi, Mohamad Bakir, Khalid S. Mohammad
Cancer Drug Resistance.2025;[Epub] CrossRef
Targeted Sequencing in Gastric Cancer: Association with Tumor Molecular Characteristics and FLOT Therapy Effectiveness
Liudmila V. Spirina, Alexandra V. Avgustinovich, Olga V. Bakina, Sergey G. Afanas’ev, Maxim Yu. Volkov, Sergey V. Vtorushin, Irina V. Kovaleva, Tatyana S. Klyushina, Igor O. Munkuev
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SLC30A2-Mediated Zinc Metabolism Modulates Gastric Cancer Progression via the Wnt/β-Catenin Signaling Pathway
Fan Li, Xiaohong Zhang, Li Feng, Xingxing Zhang
Frontiers in Bioscience-Landmark.2024;[Epub] CrossRef
Primary mucinous cystadenocarcinoma of the breast: A case report and literature review
Xi Cao, Yongchao Luo, Songjie Shen, Xinyu Ren
Oncology Letters.2024;[Epub] CrossRef

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237 Download
4 Web of Science
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