Cancer Research and Treatment

Original Articles

Korean Colorectal Cancer Screening Guidelines for Asymptomatic, average-Risk Adults: The 2025 Revision: EunKyo Kang, Jae Myung Cha, Seo Young Kang, Kiheon Lee, Su Young Kim, Younghoon Kim, An Na Seo, Hyo-Jin Kang, Jong Keon Jang, Kwang-Pil Ko, Aesun Shin, Dae Kyung Sohn, Youngki Hong, Eun-Jung Cho, Minje Han, Soo Young Kim, Hyeon Ji Lee, Chang Kyun Choi, Mina Suh; Received January 5, 2026 Accepted February 27, 2026 Published online March 13, 2026; DOI: https://doi.org/10.4143/crt.2026.014 [Accepted]

Abstract PDF: Purpose
To develop the 2025 update to the Korean colorectal cancer (CRC) screening guidelines by systematically assessing recent evidence, integrating domestic data, and addressing changes since the 2015 guideline revision, and accordingly, provide an evidence-based standard for clinicians and policymakers.
Materials and Methods
A multidisciplinary committee developed the guidelines using the Grading of Recommendations, Assessment, Development and Evaluation methodology. The process involved establishing three Key Questions (KQs) focused on efficacy, accuracy, and optimal age and interval for screening. A systematic review of international guidelines and primary literature (327 studies included) was conducted. A utility-based analysis using the Markov model was also performed to determine optimal screening ages and intervals.
Results
The review identified high-certainty evidence for Fecal Immunochemical Test (FIT) in reducing CRC mortality and moderate-certainty evidence for colonoscopy. Evidence for CT colonography (CTC) and stool DNA testing showed very low certainty. Based on this synthesis and cost-utility analysis, the committee conditionally recommends screening for asymptomatic, average-risk adults aged 45–74 years using either colonoscopy every 10 years or FIT every 1–2 years. CTC and stool DNA testing were not recommended owing to insufficient evidence.
Conclusion
The 2025 Korean Guidelines for Colorectal Cancer Screening provide the latest evidence-based recommendations tailored to the domestic context. By conditionally adopting both colonoscopy and FIT for individuals aged 45–74 years, these guidelines aim to optimize public health outcomes and reduce the colorectal cancer burden in South Korea.

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Immunosuppressive Tumor Microenvironment in Colorectal Cancer Lung Metastases: Implications for Recurrence After Metastasectomy: Minsuk Kwon, Min-Kyue Shin, Minae An, Yeong Jeong Jeon, Tae Hee Hong, Jung Kyong Shin, Sung Hee Lim, Yoonah Park, Yong Beom Cho, Seung Tae Kim, Yong Soo Choi, Jeeyun Lee; Received July 3, 2025 Accepted December 8, 2025 Published online December 17, 2025; DOI: https://doi.org/10.4143/crt.2025.691 [Accepted]

Purpose
Colorectal cancer (CRC) lung metastases exhibit high recurrence rates after resection, underscoring the need for improved therapeutic strategies. This study aimed to characterize the tumor microenvironment (TME) of CRC lung metastases and identify the factors associated with recurrence.
Materials and Methods
Fifteen CRC patients who underwent lung metastasectomy were enrolled. Multiplex immunohistochemistry (IHC), whole exome sequencing, transcriptome profiling, and single-cell RNA sequencing (scRNA-seq) were conducted on matched tumor, adjacent and distant normal lung tissues. Immune cell populations and gene expression profiles were analyzed and correlated with clinical recurrence outcomes.
Results
Exome and transcriptome analyses revealed frequent TP53, KRAS, and APC mutations. Most tumors corresponded to consensus molecular subtypes 2 and 4, characterized by immune-depleted and fibrotic features. Tumors showed downregulation of effector T and NK cell signatures. IHC revealed reduced density and increased distance of CD8+ T cells and macrophages from the epithelial cells. scRNA-seq demonstrated increased regulatory T cells and decreased NK and effector T cells in tumor. Tumor-associated macrophages (TAMs), particularly SPP1 (osteopontin)-expressing subsets, were markedly enriched in tumor and correlated with suppressed effector T cella activity. High SPP1 expression was associated with early recurrence and poor overall survival. Patients with recurrence had higher proportion of PD-1+ CD8+ T cells in adjacent normal tissues.
Conclusion
Immunosuppressive features including enrichment of SPP1+ TAMs and depletion of effector T and NK cells contribute to recurrence after CRC lung metastasectomy. Therapeutic strategies targeting both TAMs and T cells may enhance clinical outcomes in this patient population.

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Obesity promotes aggressiveness of endometrial cancer via metabolic reprogramming and intercellular crosstalk in the tumor microenvironment
Yu Chen, Yijin Fang, Guozhi Zhao, Yuanqun Zhou, Dong-Hua Yang, Jian Han, Ying Zheng
Cancer Letters.2026; 656: 218649. CrossRef

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Skeletal Muscle Index to Red Cell Distribution Width Ratio: A Novel Prognostic Indicator for Patients with Stage I-III Colorectal Cancer: Jiahn Choi, Jeonghyun Kang; Received August 15, 2025 Accepted November 12, 2025 Published online November 17, 2025; DOI: https://doi.org/10.4143/crt.2025.884 [Accepted]

Abstract PDF: Purpose
Herein, a novel prognostic marker based on the skeletal muscle index (SMI) and red cell distribution width (RDW) for patients with colorectal cancer (CRC) was developed.
Materials and Methods
585 Patients with stage I–III CRC who underwent surgery between January 2004 and April 2011 were included. The ratio of SMI to RDW (SRR) was calculated, and patients were grouped into sex-specific quartiles (G1 to G4) based on SRR. The Kaplan-Meier method was employed to estimate survival differences, and the Cox proportional hazards model was applied to evaluate the association between SRR and overall survival (OS). The Concordance Index (C-index) was calculated to assess the individual and combined effects of SMI and RDW on survival.
Results
There was a significant difference in OS across SRR quartiles (G1: 65.0%, G2: 82.9%, G3: 84.1%, G4: 89.8%, p<0.001). G1 had worse OS compared to the other groups, and SRR was confirmed as an independent prognostic factor for OS (G1 vs. G2, HR=0.531, 95% CI=0.320-0.882, p=0.014; G1 vs. G3, HR=0.534, 95% CI=0.302-0.942, p=0.030; G1 vs. G4, HR=0.419, 95% CI=0.212-0.827, p=0.012). SRR demonstrated greater prognostic power for OS than SMI or RDW alone.
Conclusion
SRR is a novel and significant predictor of overall survival in patients with stages I–III CRC demonstrating greater prognostic power than either SMI or RDW alone.

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WNT3A Upregulates the RIP1/HIF-1α/GDF-15 Pathway to Induce Epithelial-Mesenchymal Transition and Thereby Increase Colorectal Cancer Cell Migration and Invasion: A-Ram Kang, Tae-Jun Kim, Jung-Yoon Yoo, Sang-Gu Hwang, Jie-Young Song, Jong Kuk Park; Received June 16, 2025 Accepted October 17, 2025 Published online October 20, 2025; DOI: https://doi.org/10.4143/crt.2025.620 [Epub ahead of print]

Abstract PDF Supplementary Material: Purpose
We previously demonstrated that WNT signaling, a key regulator of epithelial-mesenchymal transition (EMT), promotes malignancy via receptor-interacting protein 1 (RIP1) in colorectal cancer (CRC). In this study, we aimed to reveal the novel signaling pathway through which WNT3A induces EMT in CRC.
Materials and Methods
CRC cells (DLD-1 and HCT116) and mouse embryonic fibroblasts (MEFs; wtMEF and RIP1−/− MEF) were used in this study. Expression levels of growth differentiation factor 15 (GDF-15) and GDNF receptor alpha-like (GFRAL) were assessed by reverse transcription quantitative polymerase chain reaction (RT-qPCR), immunoblotting, and enzyme-linked immunosorbent assay (ELISA). RIP1 and hypoxia-inducible factor-1α (HIF-1α) were silenced using siRNA or shRNA. Cytokine profiling and ELISA were performed to quantify GDF-15 secretion. Migration and invasion assays were conducted in GDF-15–treated cells. Expression of HIF-1α within the pathway was analyzed with RT-qPCR and immunoblotting. In vivo expressions of GDF-15 and GFRAL were detected in human blood and CRC tissue specimens.
Results
WNT3A treatment significantly upregulated both mRNA and protein levels of GDF-15 and GFRAL in CRC cells. Silencing of RIP1 with siRIP1 or shRIP1 decreased the expression and secretion of GDF-15 and GFRAL. Cytokine profiling and ELISA confirmed that RIP1 facilitates GDF-15 secretion. Treatment with GDF-15 led to enhanced cell migration, invasion, and increased EMT marker expression. We also detected increased levels of GDF-15 in blood specimens and metastatic tissues of CRC patients. Furthermore, HIF-1α was identified as a key transcription factor downstream of RIP1 that regulates GDF-15 expression.
Conclusion
Our findings demonstrate that the novel WNT3A/RIP1/HIF-1α/GDF-15 signaling axis induces EMT, migration, and invasion in CRC. This pathway might represent a potential therapeutic target for limiting metastatic progression in CRC.

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Excess Cholesterol Biosynthesis by Up-regulated HMGCS1 in Colorectal Cancer Cells Induced M2-like Tumor–Associated Macrophage Polarization via Extracellular Vesicles: Liu Yang, Bo Wu, Tingyi Sun, Haimei Sun, Jian Ma, Xiaohui Liu, Deshan Zhou, Shu Yang; Received May 22, 2025 Accepted October 11, 2025 Published online October 13, 2025; DOI: https://doi.org/10.4143/crt.2025.550 [Epub ahead of print]

Abstract PDF Supplementary Material

Purpose
The aetiology of colorectal cancer (CRC) is attributed to the intrinsic malignant cell transformation and the extrinsic tumor microenvironment (TME). Within the TME, M2-like tumor-associated macrophages (TAMs) play a pivotal role in promoting CRC malignancy. Although the interaction between tumor cells and TAMs has been studied, the mechanism underlying the polarization of M2-like TAMs directed by CRC cells remains unclear.
Materials and Methods
Macrophage polarization was analyzed by flow cytometry. Cytokine production was quantified by quantitative polymerase chain reaction. Extracellular vesicles (EVs) were identified by transmission electron microscopy and western blotting. CRC cell apoptosis and viability were measured by flow cytometry and Cell Counting Kit-8 assay, respectively.
Results
The results showed that CRC cells have high expression of 3-hydroxy-3-methylglutaryl coenzyme A synthase 1 (HMGCS1), the enzyme responsible for catalyzing the synthesis of HMG-CoA during cholesterol biosynthesis. The increased expression of HMGCS1 resulted in an excess of cholesterol in CRC patients. The excess cholesterol derived from CRC cells was released via EVs and taken up by surrounding macrophages via the CD36 receptor. Macrophages that took up CRC cell-derived cholesterol showed a preferential polarization towards M2-like TAMs, which produced large amounts of pro-tumor cytokines. The production of these cytokines further accelerated the progression of the surrounding CRC.
Conclusion
Our findings revealed a mutual stimulatory effect between CRC cells and M2-like TAMs. CRC cells with hyper-expressed HMGCS1 facilitated M2-like TAM polarization by releasing cholesterol-rich EVs, and M2-like TAMs in turn promoted CRC malignancy. These findings suggest that inhibiting excessive cholesterol production may be a promising strategy for the treatment of advanced CRC.

Citations

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Exosomal crosstalk between breast cancer cells and tumor-associated macrophages: mechanisms and therapeutic implications
Rong-quan Gong, An Xu, Xiao Huang, Deyuan Fu
Molecular Biology Reports.2026;[Epub] CrossRef
Metabolic Messengers: Extracellular Vesicles as Central Mediators of Metabolic Reprogramming in Renal Cell Cancer
Qingshu Meng, Liqun Huang, Zhiguo Chen, Rui Lin, Xiaohui Zhou, Guosheng Yang
Biomedicines.2026; 14(2): 282. CrossRef
USP16 promotes M2 polarization of macrophages in colorectal cancer by activating the Notch pathway via inducing the deubiquitination of E2F1
Hua Yu, Mengmeng Chen, Boxu Chen, Shiwei Hu, Xiaoyu Dai
Cytotechnology.2026;[Epub] CrossRef
Parallel Alterations in Gut and Tumor Microbiota in Pediatric Oncology: Potential Impacts on Disease Progression and Treatment Response
Patrik József Szabó, Viktória Sági, Levente Károly Kassai, Renáta Mária Kiss-Miki, Nóra Makra, Dóra Szabó, Miklós Garami
Cancers.2025; 17(21): 3426. CrossRef

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Gastrointestinal cancer

Molecular Mosaics: Unveiling Heterogeneity in Synchronous Colorectal Cancers: Hyun Gu Lee, Yeseul Kim, Mi-Ju Kim, Yeon Wook Kim, Sun-Young Jun, Deokhoon Kim, In Ja Park, Seung-Mo Hong; Cancer Res Treat. 2026;58(1):264-274. Published online February 18, 2025; DOI: https://doi.org/10.4143/crt.2024.947

Abstract PDF Supplementary Material PubReader ePub: Purpose
Molecular characteristics of synchronous colorectal cancers (SCRCs) remain incompletely elucidated, despite their importance in targeted therapy selection. We compared the molecular characteristics and somatic mutations between SCRCs.
Materials and Methods
This retrospective study (2012-2014) included 98 consecutive patients with surgically resected SCRCs. Molecular characteristics, including microsatellite instability (MSI) and tumor-infiltrating lymphocytes (TILs), were analyzed for all cancer lesions. The intertumoral heterogeneity of SCRCs was evaluated using whole-exome sequencing (WES) for 18 cancers from nine patients with at least one MSI-high (MSI-H) tumor.
Results
Twelve patients had at least one MSI-H tumor; five showed discordant MSI status. Mucinous adenocarcinoma frequency and TIL density were higher in patients with at least one MSI-H tumor than in those with only microsatellite-stable tumors. WES revealed that, except one patient (6.5%), most synchronous cancers shared few variants in each patient (0.09%-0.36%). The concordance rates for BRAF, KRAS, NRAS, and PIK3CA, in synchronous cancers from each patient were 66.7%, 66.7%, 66.7%, and 55.6%, respectively.
Conclusion
Although synchronous cancers shared a mutated gene, the mutation subtypes differed. SCRCs exhibited 5.1% MSI status discordance rate and a high discordance rate in somatic mutational variants. As intertumoral heterogeneity may affect the targeted therapy response, molecular analysis of all tumors is recommended for patients with SCRCs.

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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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Gastrointestinal cancer

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; Cancer Res Treat. 2025;57(4):1135-1143. Published online February 6, 2025; DOI: https://doi.org/10.4143/crt.2024.1040

Abstract PDF Supplementary Material PubReader ePub

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
A total of 404 patients 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.

Citations

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Percutaneous Cryoablation Under Local Anesthesia for Pulmonary Metastases From Colorectal Cancer: Long‐Term Outcomes From a Single‐Institution Retrospective Cohort
Shun Yorimori, Kaoru Kaseda, Yusuke Aoki, Kosuke Sugino, Takahiro Suzuki, Yu Okubo, Shigeki Suzuki, Kyohei Masai, Masashi Tamura, Masanori Inoue, Hideki Yashiro, Seishi Nakatsuka, Yoshikane Yamauchi, Yotaro Izumi, Masafumi Kawamura, Masahiro Jinzaki, Keis
Cancer Reports.2026;[Epub] CrossRef
Emerging Applications of Stereotactic Ablative Radiotherapy in Oligometastatic Colorectal Cancer
Hasan Al-Sattar, Esele Okondo, Amir Mashia Jaafari, Inesh Sood, Jakob Hassan Dinif, Su Yin Lim, Charlotte Hafkamp, Irene Chong, Joao R. Galante, Sola Adeleke
International Journal of Molecular Sciences.2025; 26(21): 10302. CrossRef

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The Roles of Ninjurin1 and Estrogen in Modulating Azoxymethane/Dextran Sodium Sulfate–Induced Colitis-Associated Colorectal Cancer in Male Mice: Chin-Hee Song, Nayoung Kim, Ryoung Hee Nam, Jae Young Jang, Eun Hye Kim, Sungchan Ha, Eun Shin, Ha-Na Lee, Hoon Choi, Kyu-Won Kim, Sejin Jeon, Goo Taeg Oh; Cancer Res Treat. 2025;57(4):1115-1134. Published online January 13, 2025; DOI: https://doi.org/10.4143/crt.2024.959

Abstract PDF PubReader ePub: Purpose
Nerve injury–induced protein 1 (Ninj1) is associated with inflammation and tumor progression and shows increased expression in various cancers. This study aimed to investigate the role of Ninj1 in colitis-associated colorectal cancer (CRC) by focusing on its interaction with 17β-estradiol (E2).
Materials and Methods
Using an azoxymethane (AOM)/dextran sodium sulfate (DSS) mouse model of colitis-associated CRC, wild-type (WT) and Ninj1 knockout (KO) male mice were treated with or without E2.
Results
At week 2, Ninj1 KO mice exhibited attenuated colitis symptoms than WT mice following AOM/DSS treatment. E2 administration significantly alleviated these symptoms in both WT and Ninj1 KO mice, with reductions in the disease activity index, colon length shortening, and histopathological damage. The levels of pro-inflammatory mediators were reduced by E2 treatment in both groups, with the Ninj1 KO group showing a more pronounced response. At week 13, tumor development in Ninj1 KO mice was significantly lower than that in WT mice, particularly in the distal colon. E2 treatment inhibited tumor formation in WT mice and had a stronger inhibitory effect on distal colon tumorigenesis in Ninj1 KO mice. Immune cell populations, including the populations of macrophages and T cells, were also modulated by E2 in WT mice; however, these effects were diminished in Ninj1 KO mice.
Conclusion
These findings suggest that Ninj1 plays a role in modulating colitis and CRC progression, with E2 exerting anti-inflammatory and anti-tumorigenic effects that are influenced by Ninj1 status.

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Clinical Characteristics of and Treatment Pattern for EGFR-Amplified Colorectal Cancer: Seong-Eun Kim, Hyehyun Jeong, Sun Young Kim, Jeong Eun Kim, Yong Sang Hong, Deokhoon Kim, Jihun Kim, Ji Sung Lee, Tae Won Kim; Cancer Res Treat. 2025;57(4):1104-1114. Published online January 10, 2025; DOI: https://doi.org/10.4143/crt.2024.569

Abstract PDF Supplementary Material PubReader ePub: Purpose
This study aimed to compare clinicopathologic features and clinical outcomes of metastatic colorectal cancer (mCRC) based on epidermal growth factor receptor (EGFR) amplification status.
Materials and Methods
Patients with mCRC who underwent next-generation sequencing using a targeted 244-gene panel from 2016 to 2021 were identified and screened for EGFR copy numbers. Cases with at least five copies were reviewed for tumor purity adjustment, and those with an adjusted copy number of ≥ 6 were defined as EGFR-amplified (EGFR amp+). Their clinical characteristics were compared with those without EGFR amplification (EGFR amp–).
Results
Among 2,421 patients, 35 (1.4%) were EGFR amp+. Clinical characteristics did not significantly differ according to EGFR amplification status, but EGFR amp+ cases had fewer instances of peritoneal seeding (8.6% vs. 21.8%). Overall survival (OS) tended to be better in EGFR amp+ patients compared with EGFR amp– patients (median OS [mOS], 76 vs. 37 months; p=0.145). Among 572 patients who received anti-EGFR antibody–based chemotherapy (anti-EGFR CTx) during disease course, mOS tended to be better in 16 EGFR amp+ patients (79 months) compared with 556 EGFR amp– patients (39 months, p=0.048). Seven out of 35 EGFR amp+ patients were treated with front-line anti-EGFR CTx, and their progression-free survival did not differ from that of EGFR amp– patients treated with front-line anti-EGFR CTx (20 vs. 14 months, p=0.344).
Conclusion
This study may suggest a favorable predictive impact of EGFR amplification in patients treated with anti-EGFR CTx. However, the benefit of front-line anti-EGFR antibody treatment in this group was not notable.

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Is Colonoscopy Alone Adequate for Surveillance in Stage I Colorectal Cancer?: Seijong Kim, Jung Kyong Shin, Yoonah Park, Jung Wook Huh, Hee Cheol Kim, Seong Hyeon Yun, Woo Yong Lee, Yong Beom Cho; Cancer Res Treat. 2025;57(2):507-518. Published online October 4, 2024; DOI: https://doi.org/10.4143/crt.2024.526

Abstract PDF PubReader ePub

Purpose
While colonoscopy is the standard surveillance tool for stage I colorectal cancer according to National Comprehensive Cancer Network guidelines, its effectiveness in detecting recurrence is debated. This study evaluates recurrence risk factors and patterns in stage I colorectal cancer to inform comprehensive surveillance strategies.
Materials and Methods
A retrospective analysis of 2,248 stage I colorectal cancer patients who underwent radical surgery at Samsung Medical Center (2007-2018) was conducted. Exclusions were based on familial history, prior recurrences, preoperative treatments, and inadequate data. Surveillance included colonoscopy, laboratory tests, and computed tomography (CT) scans.
Results
Stage I colorectal cancer patients showed favorable 5-year disease-free survival (98.3% colon, 94.6% rectum). Among a total of 1,467 colon cancer patients, 26 (1.76%) experienced recurrence. Of the 781 rectal cancer patients, 47 (6.02%) experienced recurrence. Elevated preoperative carcinoembryonic antigen levels and perineural invasion were significant recurrence risk factors in colon cancer, while tumor budding was significant in rectal cancer. Distant metastasis was the main recurrence pattern in colon cancer (92.3%), while rectal cancer showed predominantly local recurrence (50%). Colonoscopy alone detected recurrences in a small fraction of cases (3.7% in colon, 14.9% in rectum).
Conclusion
Although recurrence in stage I colorectal cancer is rare, relying solely on colonoscopy for surveillance may miss distant metastases or locoregional recurrence outside the colorectum. For high-risk patients, we recommend considering regular CT scans alongside colonoscopy. This targeted approach may enable earlier recurrence detection and improve outcomes in this subset while avoiding unnecessary scans for the low-risk majority.

Citations

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Randomized Controlled Trial Evaluating the Safety, Efficacy, and Patient Comfort of a Single‐Use Electronic Colonoscope
Yuan Tian, Xiaolong Rao, Hang Yu, Lingfeng Zheng, Ao Wang, Shuangjiao Liu, Yan He, Long Rong
Journal of Gastroenterology and Hepatology.2026; 41(6): 1751. CrossRef
Beyond “High Risk”: Toward Individualized Decision-Making After Noncurative Endoscopic Resection of T1 Colorectal Cancer
Fredy Nehme, Phillip S. Ge
Annals of Surgical Oncology.2026;[Epub] CrossRef
Enhancing and Not Replacing Clinical Expertise: Improving Named-Entity Recognition in Colonoscopy Reports Through Mixed Real–Synthetic Training Sources
Andrei-Constantin Ioanovici, Andrei-Marian Feier, Marius-Ștefan Mărușteri, Alina-Dia Trâmbițaș-Miron, Daniela-Ecaterina Dobru
Journal of Personalized Medicine.2025; 15(8): 334. CrossRef
Incidence and Risk Factors of Pulmonary Metastasis as the Initial Site of Metastasis After Surgical Resection for Rectal Cancer by TNM Stage
Misol Do, Seijong Kim, Woo Yong Lee, Seong Hyeon Yun, Hee Cheol Kim, Yong Beom Cho, Jung Wook Huh, Yoon Ah Park, Jung Kyong Shin
Diseases of the Colon & Rectum.2025; 68(11): 1285. CrossRef

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2 Web of Science
4 Crossref

The Oncogenic Role of TNFRSF12A in Colorectal Cancer and Pan-Cancer Bioinformatics Analysis: Chuyue Wang, Yingying Zhao, You Chen, Ying Shi, Zhiying Yang, Weili Wu, Rui Ma, Bo Wang, Yifeng Sun, Ping Yuan; Cancer Res Treat. 2025;57(1):212-228. Published online August 9, 2024; DOI: https://doi.org/10.4143/crt.2024.408

Abstract PDF Supplementary Material PubReader ePub

Purpose
Cancer has become a significant major public health concern, making the discovery of new cancer markers or therapeutic targets exceptionally important. Elevated expression of tumor necrosis factor receptor superfamily member 12A (TNFRSF12A) expression has been observed in certain types of cancer. This project aims to investigate the function of TNFRSF12A in tumors and the underlying mechanisms.
Materials and Methods
Various websites were utilized for conducting the bioinformatics analysis. Tumor cell lines with stable knockdown or overexpression of TNFRSF12A were established for cell phenotyping experiments and subcutaneous tumorigenesis in BALB/c mice. RNA-seq was employed to investigate the mechanism of TNFRSF12A.
Results
TNFRSF12A was upregulated in the majority of cancers and associated with a poor prognosis. Knockdown TNFRSF12A hindered the colorectal cancer progression, while overexpression facilitated malignancy both in vitro and in vivo. TNFRSF12A overexpression led to increased nuclear factor кB (NF-κB) signaling and significant upregulation of baculoviral IAP repeat containing 3 (BIRC3), a transcription target of the NF-κB member RELA, and it was experimentally confirmed to be a critical downstream factor of TNFRSF12A. Therefore, we speculated the existence of a TNFRSF12A/RELA/BIRC3 regulatory axis in colorectal cancer.
Conclusion
TNFRSF12A is upregulated in various cancer types and associated with a poor prognosis. In colorectal cancer, elevated TNFRSF12A expression promotes tumor growth, potentially through the TNFRSF12A/RELA/BIRC3 regulatory axis.

Citations

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Superenhancers shape the landscape and repair dynamics of transcription-associated DNA breaks in cancer
Osama Hidmi, Diala Shatleh, Sara Oster Flayshman, Jonathan Monin, Rami I. Aqeilan
Science Advances.2026;[Epub] CrossRef
SLC12A7 serves as a prognostic and immunotherapeutic biomarker identified by multi-omics analysis
Haoran Qu, Jun Sun, Guohao Wang, Shuhong Ding, Xiaoming Li
Frontiers in Immunology.2026;[Epub] CrossRef
Investigating the Role of TNFSF12 in Thyroid Cancer Progression via Single‐Cell RNA Sequencing and Integrated Multiomics Analyses
Junjie Yu, Jingjing Li, Shengnan Gao, Lilan Wang, Hong Qiao, Liu Jinhui
Mediators of Inflammation.2026;[Epub] CrossRef
TNFRSF12A expression in stomach adenocarcinoma and its preliminary role in predicting immunotherapy response
Lin-De Sun, Lin-Lin Zhang, Zheng Wan, Xiao-Dong Yang, Jing Yao, Ze-Long Yang, Lin Liu, Jun-Yan Liu
Frontiers in Immunology.2025;[Epub] CrossRef
TRUB1 is a novel biomarker for promoting malignancy in colorectal cancer via NFκB signaling
Yingzhao Wang, Yonghuang Tan, Tianhao Zhang, Zhaoliang Wang, Jingru Gong, Zhenshuang Du, Yong Mei, Jinping Ma
Gastroenterology Report.2025;[Epub] CrossRef
Over-Expression of TNFRSF12A Promotes Immune Suppression and Facilitates Angiogenesis in Triple-Negative Breast Cancer
Can Jiang, Zhengwei Zhou, Guang Shu, Gang Yin, Maonan Wang
Biology.2025; 14(11): 1513. CrossRef
The Exosome-Mediated Epigenome: Non-Coding RNA and mRNA-Coding Networks in Microbiome–Cellular Communication, Inflammation, and Tumorigenesis Along the Oral–Gut–Lung Axis
Beatriz Andrea Otálora-Otálora, César Payán-Gómez, Juan Javier López-Rivera, Luisa Fernanda Patiño-Unibio, Sally Lorena Arboleda-Mojica, Claudia Aristizábal-Guzmán, Mario Arturo Isaza-Ruget, Carlos Arturo Álvarez-Moreno
Epigenomes.2025; 9(4): 52. 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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Original Articles

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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Association analysis of the differences in intestinal flora and clinical tumor indicators among colorectal cancer patients
Lijun Ma, Wenjing Wang, Shihu Ma, Yanbai Wang, Hai Li, Ying Gao, Xiaoliang Xie
Frontiers in Cellular and Infection Microbiology.2026;[Epub] CrossRef
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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Longitudinal Comparative Analysis of Circulating Tumor DNA and Matched Tumor Tissue DNA in Patients with Metastatic Colorectal Cancer Receiving Palliative First-Line Systemic Anti-Cancer Therapy: Seung-been Lee, Ji-Won Kim, Hong-Geun Kim, Sung-Hyun Hwang, Kui-Jin Kim, Ju Hyun Lee, Jeongmin Seo, Minsu Kang, Eun Hee Jung, Koung Jin Suh, Se Hyun Kim, Jin Won Kim, Yu Jung Kim, Jee Hyun Kim, Nak-Jung Kwon, Keun-Wook Lee; Cancer Res Treat. 2024;56(4):1171-1182. Published online April 29, 2024; DOI: https://doi.org/10.4143/crt.2024.016

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study aimed to compare tumor tissue DNA (ttDNA) and circulating tumor DNA (ctDNA) to explore the clinical applicability of ctDNA and to better understand clonal evolution in patients with metastatic colorectal cancer undergoing palliative first-line systemic therapy.
Materials and Methods
We performed targeted sequencing analysis of 88 cancer-associated genes using germline DNA, ctDNA at baseline (baseline-ctDNA), and ctDNA at progressive disease (PD-ctDNA). The results were compared with ttDNA data.
Results
Among 208 consecutively enrolled patients, we selected 84 (41 males; median age, 59 years; range, 35 to 90 years) with all four sample types available. A total of 202 driver mutations were found in 34 genes. ttDNA exhibited the highest mutation frequency (n=232), followed by baseline-ctDNA (n=155) and PD-ctDNA (n=117). Sequencing ctDNA alongside ttDNA revealed additional mutations in 40 patients (47.6%). PD-ctDNA detected 13 novel mutations in 10 patients (11.9%) compared to ttDNA and baseline-ctDNA. Notably, seven mutations in five patients (6.0%) were missense or nonsense mutations in APC, TP53, SMAD4, and CDH1 genes. In baseline-ctDNA, higher maximal variant allele frequency (VAF) values (p=0.010) and higher VAF values of APC (p=0.012), TP53 (p=0.012), and KRAS (p=0.005) mutations were significantly associated with worse overall survival.
Conclusion
While ttDNA remains more sensitive than ctDNA, our ctDNA platform demonstrated validity and potential value when ttDNA was unavailable. Post-treatment analysis of PD-ctDNA unveiled new pathogenic mutations, signifying cancer’s clonal evolution. Additionally, baseline-ctDNA’s VAF values were prognostic after treatment.

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Liquid biopsy in precision oncology: Current insights and future perspectives
Rajalakshmi Geetha, Subramania Iyer
Indian Journal of Precision Medicine and Molecular Medicine.2026; 2(1): 22. CrossRef
Metastatic Odyssey: Decoding the Genomic Journey from Primary Colorectal Cancer to Disseminated Disease
Taxiarchis Konstantinos Nikolouzakis, John Souglakos, Epameinondas Evangelos Kantidakis, Katerina Achilleos, Troye van Staden, Emmanuel Chrysos
Cancers.2026; 18(7): 1062. CrossRef
Precision-Guided Durable Response From Venetoclax With Decitabine in a Patient With a Metastatic Refractory IDH2 -Mutant Cholangiocarcinoma
Eylül Özgü, Ünal Metin Tokat, Ashkan Adibi, Şevval Nur Bilgiç, Esranur Aydın, Onur Tutar, Mutlu Demiray
JCO Precision Oncology.2025;[Epub] CrossRef
Evolution of Neo-RAS-WT in Circulating Tumor DNA from First-Line to Subsequent Therapies in Metastatic Colorectal Cancer
Marco Siringo, Michela De Meo, Irene Bottillo, Paola Grammatico, Enrico Cortesi, Chiara Nicolazzo, Paola Gazzaniga
Cancers.2025; 17(7): 1070. CrossRef
Liquid biopsy in gastrointestinal oncology: clinical applications and translational integration of ctDNA, CTCs, and sEVs
Rita Palieri, Maria De Luca, Francesco Balestra, Giorgia Panzetta, Claudio Lotesoriere, Federica Rizzi, Angela Dalia Ricci, Rita Mastrogiacomo, Maria Lucia Curri, Luigi Andrea Laghi, Gianluigi Giannelli, Nicoletta Depalo, Maria Principia Scavo
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Circulating Tumor DNA as a Biomarker for Precision Medicine in Prostate Cancer: A Systematic Review
Nouhaila Chanhih, Abdelilah Laraqui, Salma Hassine, Ahmed Ameur, Larbi Hamedoun, Hicham El Annaz, Rachid Abi, Mohamed Rida Tagajdid, Idriss Lahlou Amine, Khalid Ennibi, Abdelaziz Benjouad, Lamiae Belayachi
International Journal of Molecular Sciences.2025; 26(22): 11049. CrossRef

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Association between Endoscopist Volume and Interval Cancers after Colonoscopy: Results from the National Colorectal Cancer Screening Program in Korea: Dong Jun Kim, Nan-He Yoon, Jae Kwan Jun, Mina Suh, Sunhwa Lee, Seongju Kim, Ji Eun Kim, Hooyeon Lee; Cancer Res Treat. 2024;56(4):1164-1170. Published online April 16, 2024; DOI: https://doi.org/10.4143/crt.2024.009

Abstract PDF Supplementary Material PubReader ePub

Purpose
The rate of interval colorectal cancer (iCRC) is now accepted as a key performance indicator of organized colorectal cancer (CRC) screening programs. We aimed to examine the association between endoscopist volumes and the rate of iCRC among individuals with a positive fecal immunochemical test (FIT) within a nationwide population-based CRC screening program.
Materials and Methods
Individuals aged ≥ 50 years who underwent colonoscopy after a positive FIT from January 1, 2019 until December 31, 2020 in the Korean National Cancer Screening Program (KNCSP) were enrolled. We converted the data into per-endoscopist screening results, calculated the iCRC rates per endoscopist, and compared them to the previous year’s annual volume that was divided into five groups (V1, 1-9; V2, 10-29; V3, 30-59; V4, 60-119; V5, ≥ 120).
Results
A total of 10,412 endoscopists performed 216,907 colonoscopies. Overall, the average rate of iCRC per endoscopist was 8.46 per 1,000 examinations. Compared with the group with the highest volume (V5 group), the rate of iCRC was 2.21 times higher in the V1 group. Similar trends were observed in the other groups (V2: relative risks [RR], 2.15; 95% confidence interval [CI], 1.57 to 2.94; V3: RR, 1.56; 95% CI, 1.15 to 2.13; V4: RR, 1.18; 95% CI, 0.83 to 1.67).
Conclusion
The findings emphasize that endoscopists with lower procedure volumes have higher risks of interval cancer being missed or undetected. To maximize the preventative impact of colonoscopy for CRC, this issue should be addressed by monitoring endoscopist volumes and variations in performances.

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Biennial Mammography Performance in the Korean National Cancer Screening Program From 2009 to 2020
Dong Jun Kim, Nan-He Yoon, Jae Kwan Jun, Mina Suh, Sunhwa Lee, Seongju Kim, Horim A. Hwang, Seung Eun Jung, Hooyeon Lee
Korean Journal of Radiology.2025; 26(4): 313. CrossRef
Preliminary reports of lung cancer screening with low-dose computed tomography: a nationwide performance on the Korean population in 2019–2020
Horim A. Hwang, Dong Jun Kim, Nan-He Yoon, Jae Kwan Jun, Mina Suh, Sunhwa Lee, Seongju Kim, Seung Eun Jung, Hooyeon Lee
European Radiology.2025; 35(9): 5492. CrossRef

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The Persistence of Hypertriglyceridemia and the Risk of Early Onset Colorectal Cancer According to Tumor Subsites: A Nationwide Population-Based Study: Young Hoon Chang, Cheol Min Shin, Kyungdo Han, Jin Hyung Jung, Eun Hyo Jin, Joo Hyun Lim, Seung Joo Kang, Yoon Jin Choi, Hyuk Yoon, Young Soo Park, Nayoung Kim, Dong Ho Lee; Cancer Res Treat. 2024;56(3):825-837. Published online December 20, 2023; DOI: https://doi.org/10.4143/crt.2023.753

Abstract PDF Supplementary Material PubReader ePub

Purpose
The incidence of early-onset colorectal cancer (EoCRC) is increasing worldwide. The association between hypertriglyceridemia (HTG) and EoCRC risk remains unclear.
Materials and Methods
We conducted a nationwide cohort study of 3,340,635 individuals aged 20-49 years who underwent health checkups between 2009 and 2011 under the Korean National Health Insurance Service. HTG was defined as serum triglyceride (TG) level ≥ 150 mg/dL. According to the change in TG status, participants were categorized into persistent normotriglyceridemia (NTG; group 1), NTG to HTG (group 2), HTG to NTG (group 3), and persistent HTG (group 4) groups. The EoCRC incidence was followed up until 2019.
Results
In total, 7,492 EoCRC cases developed after a mean of 6.05 years of follow-up. Group 4 had the highest risk of EoCRC (adjusted hazard ratio [aHR], 1.097; 95% confidence interval [CI], 1.025 to 1.174). While the risk of rectal cancer was significantly increased in groups 3 and 4 (aHR [95% CI], 1.236 [1.076 to 1.419] and 1.175 [1.042-1.325], respectively), no significant risk differences were observed in right colon cancer. In group 4, male sex and diabetes were associated with a further increased risk of EoCRC (aHR [95% CI], 1.149 [1.082 to 1.221] and 1.409 [1.169 to 1.699], respectively). In addition, there was a dose-response relationship between serum TG levels and the risk of EoCRC (p for trends < 0.0001).
Conclusion
Persistent HTG increased the risk of EoCRC, which was significantly higher only for rectal cancer and marginally higher for other colonic subsites.

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The association between serum triglycerides and colorectal cancer incidence in community-dwelling middle-aged and older adults in Korea: a secondary analysis of a community-based prospective cohort
Bo-Kyoung Cha
Journal of Korean Biological Nursing Science.2026; 28(1): 119. CrossRef
Systemic inflammation mediates the link between metabolic syndrome and colorectal cancer risk: insights from a large prospective cohort
Wenwen Lv, Suna Wang, Lei Duan, Zhongxun Dong, Hai Zhu, Gang Wang, Zhangsheng Yu, Shuhua Xu
Postgraduate Medical Journal.2026;[Epub] CrossRef
Risk Factors for Early-Onset Colorectal Cancer: A Nested Case‒Control Study within the Korean National Health Insurance Service‒Health Screening Cohort
Ji Yoon Baek, Seung-Yong Jeong, Aesun Shin
Cancer Epidemiology, Biomarkers & Prevention.2026; 35(4): 647. CrossRef
High-fat diet, triglyceride glucose index, and gastrointestinal cancer: integrative insights from human and animal studies
Jinmei Li, Zi Dai, Yinping Cai, Ye Wu, Yalan Wu, Cantu Fang, Yao Wang
Frontiers in Nutrition.2026;[Epub] CrossRef
Risk Factors in Sporadic Early-Onset Colorectal Cancer, Current Evidence and Emerging Insights: A Systematic Review
Meghana Maddula, Jordan E. Cohen, Dulitha Kumarasinghe, Mandy L. Ballinger, Jaqueline L. E. Tearle, Kylie R. James, Adnan Nagrial, Megan Barnet, Subotheni Thavaneswaran
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Elena Crecca, Gianfranco Di Giuseppe, Claudia Camplone, Virginia Vigiano Benedetti, Ombretta Melaiu, Teresa Mezza, Chiara Cencioni, Francesco Spallotta
Pharmacology & Therapeutics.2025; 270: 108847. CrossRef
Obesity-Associated Colorectal Cancer
Lucia Gonzalez-Gutierrez, Omar Motiño, Daniel Barriuso, Juan de la Puente-Aldea, Lucia Alvarez-Frutos, Guido Kroemer, Roberto Palacios-Ramirez, Laura Senovilla
International Journal of Molecular Sciences.2024; 25(16): 8836. CrossRef

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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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A Phase 1b/2a Study of GC1118 with 5-Fluorouracil, Leucovorin and Irinotecan (FOLFIRI) in Patients with Recurrent or Metastatic Colorectal Cancer: Keun-Wook Lee, Sae-Won Han, Tae Won Kim, Joong Bae Ahn, Ji Yeon Baek, Sang Hee Cho, Howard Lee, Jin Won Kim, Ji-Won Kim, Tae-You Kim, Yong Sang Hong, Seung-Hoon Beom, Yongjun Cha, Yoonjung Choi, Seonhui Kim, Yung-Jue Bang; Cancer Res Treat. 2024;56(2):590-601. Published online December 7, 2023; DOI: https://doi.org/10.4143/crt.2023.1117

Abstract PDF Supplementary Material PubReader ePub

Purpose
GC1118 is a novel antibody targeting epidermal growth factor receptor (EGFR) with enhanced blocking activity against both low- and high-affinity EGFR ligands. A phase 1b/2a study was conducted to determine a recommended phase 2 dose (RP2D) of GC1118 in combination with 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI) (phase 1b) and to assess the safety and efficacy of GC1118 plus FOLFIRI as a second-line therapy for recurrent/metastatic colorectal cancer (CRC) (phase 2a).
Materials and Methods
Phase 1b was designed as a standard 3+3 dose-escalation study with a starting dose of GC1118 (3 mg/kg/week) in combination with biweekly FOLFIRI (irinotecan 180 mg/m²; leucovorin 400 mg/m²; 5-fluorouracil 400 mg/m² bolus and 2,400 mg/m² infusion over 46 hours) in patients with solid tumors refractory to standard treatments. The subsequent phase 2a part was conducted with objective response rate (ORR) as a primary endpoint. Patients with KRAS/NRAS/BRAF wild-type, EGFR-positive, recurrent/metastatic CRC resistant to the first-line treatment were enrolled in the phase 2a study.
Results
RP2D of GC1118 was determined to be 3 mg/kg/wk in the phase 1b study (n=7). Common adverse drug reactions (ADRs) observed in the phase 2a study (n=24) were acneiform rash (95.8%), dry skin (66.7%), paronychia (58.3%), and stomatitis (50.0%). The most common ADR of ≥ grade 3 was neutropenia (33.3%). ORR was 42.5% (95% confidence interval [CI], 23.5 to 62.0), and median progression-free survival was 6.7 months (95% CI, 4.0-8.0).
Conclusion
GC1118 administered weekly at 3 mg/kg in combination with FOLFIRI appears as an effective and safe treatment option in recurrent/metastatic CRC.

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Drug resistance-driven cytokine alterations in the immunosuppressive microenvironment of colorectal cancer
Yingying Shao, Zewen Zhang, Yu Wang, Chunze Zhang, Erwei Liu, Haiyang Yu
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Drug combinations of camptothecin derivatives promote the antitumor properties
Zhen Liu, Yajie Yuan, Ning Wang, Peng Yu, Yuou Teng
European Journal of Medicinal Chemistry.2024; 279: 116872. CrossRef

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Differential Perspectives by Specialty on Oligometastatic Colorectal Cancer: A Korean Oligometastasis Working Group’s Comparative Survey Study: Won Kyung Cho, Gyu Sang Yoo, Chai Hong Rim, Jae-Uk Jeong, Eui Kyu Chie, Yong Chan Ahn, Hyeon-Min Cho, Jun Won Um, Yang-Gun Suh, Ah Ram Chang, Jong Hoon Lee, On behalf of the Oligometastasis Working Group, Korean Cancer Association; Cancer Res Treat. 2023;55(4):1281-1290. Published online June 7, 2023; DOI: https://doi.org/10.4143/crt.2023.479

Abstract PDF PubReader ePub

Purpose
Despite numerous studies on the optimal treatments for oligometastatic disease (OMD), there is no established interdisciplinary consensus on its diagnosis or classification. This survey-based study aimed to analyze the differential opinions of colorectal surgeons and radiation oncologists regarding the definition and treatment of OMD from the colorectal primary.
Materials and Methods
A total of 141 participants were included in this study, consisting of 63 radiation oncologists (44.7%) and 78 colorectal surgeons (55.3%). The survey consisted of 19 questions related to OMD, and the responses were analyzed using the chi-square test to determine statistical differences between the specialties.
Results
The radiation oncologists chose “bone” more frequently compared to the colorectal surgeons (19.2% vs. 36.5%, p=0.022), while colorectal surgeons favored “peritoneal seeding” (26.9% vs. 9.5%, p=0.009). Regarding the number of metastatic tumors, 48.3% of colorectal surgeons responded that “irrelevant, if all metastatic lesions are amendable to local therapy”, while only 21.8% of radiation oncologist chose same answer. When asked about molecular diagnosis, most surgeons (74.8%) said it was important, but only 35.8% of radiation oncologists agreed.
Conclusion
This study demonstrates that although radiation oncologists and colorectal surgeons agreed on a majority of aspects such as diagnostic imaging, biomarker, systemic therapy, and optimal timing of OMD, they also had quite different perspectives on several aspects of OMD. Understanding these differences is crucial to achieving multidisciplinary consensus on the definition and optimal management of OMD.

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Regional differences in surgical strategies for peritoneal metastases based on various perspectives on oligometastases
Toshiyuki Kitai, Kenya Yamanaka, Ben Sasaki, Akie Tani, Yusuke Mishima, Takahito Omine, Makoto Kurimoto, Yuki Mochida, Masaki Tani, Kosuke Toda, Takefumi Yazawa, Hidenori Ohe, Masahiro Yamada
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Eui Kyu Chie, Chai Hong Rim, Won Kyung Cho, Yong Chan Ahn
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Clinical Significance of Combining Preoperative and Postoperative Albumin-Bilirubin Score in Colorectal Cancer: Doyoun Kim, Jae-Hoon Lee, Eun-Suk Cho, Su-Jin Shin, Hye Sun Lee, Hwa-Hee Koh, Kang Young Lee, Jeonghyun Kang; Cancer Res Treat. 2023;55(4):1261-1269. Published online April 17, 2023; DOI: https://doi.org/10.4143/crt.2022.1444

Abstract PDF Supplementary Material PubReader ePub

Purpose
Albumin-bilirubin (ALBI) score is a well-known prognostic factor for various diseases, including colorectal cancer (CRC). However, little is known about the significance of postoperative ALBI score changes in patients with CRC.
Materials and Methods
A total of 723 patients who underwent surgery were enrolled. Preoperative ALBI (ALBI-pre) and postoperative ALBI (ALBI-post) scores were divided into low and high score groups. ALBI-trend was defined as a combination of four groups comprising the low and high ALBI-pre and ALBI-post score groups. Kaplan-Meier survival curves were used to compare the overall survival (OS) between the different ALBI groups. The Cox proportional hazards model was used to examine the independent relevant factors of OS. Stratification performance was compared between the different ALBI groupings using Harrell’s concordance index (C-index).
Results
ALBI-pre, ALBI-post, and ALBI-trend score groups were significant prognostic factors of OS in the univariable analysis. However, multivariable analysis showed that ALBI-trend was an independent prognostic factor while ALBI-pre and ALBI-post were not. The C-index of ALBI-trend (0.622; 95% confidence interval [CI], 0.587 to 0.655) was higher than that of ALBI-pre (0.589; 95% CI, 0.557 to 0.621; bootstrap mean difference, 0.033; 95% CI, 0.013 to 0.057) and ALBI-post (0.575; 95% CI, 0.545 to 0.605; bootstrap mean difference, 0.047; 95% CI, 0.024 to 0.074).
Conclusion
Combining ALBI-pre and ALBI-post scores is an independent prognostic factor of OS and shows superior predictive power compared to ALBI-pre or ALBI-post alone in patients with CRC.

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Review Article

Metastasis-Directed Local Therapy of Hepatic Oligometastasis from Colorectal Cancer and Future Perspective in Radiation Therapy: Gyu Sang Yoo, Chai Hong Rim, Won Kyung Cho, Jae-Uk Jeong, Eui Kyu Chie, Hyeon-Min Cho, Jun Won Um, Yong Chan Ahn, Jong Hoon Lee, on behalf of Korean Cancer Association Oligometastasis Working Group; Cancer Res Treat. 2023;55(3):707-719. Published online March 15, 2023; DOI: https://doi.org/10.4143/crt.2022.1599

Abstract PDF PubReader ePub

Introduction of the concept for oligometastasis led to wide application of metastasis-directed local ablative therapies for metastatic colorectal cancer (CRC). By application of the metastasis-directed local ablative therapies including surgical resection, radiofrequency ablation (RFA), and stereotactic ablative body radiotherapy (SABR), the survival outcomes of patients with metastatic CRC have improved. The liver is the most common distant metastatic site in CRC patients, and recently various metastasis-directed local therapies for hepatic oligometastasis from CRC (HOCRC) are widely used. Surgical resection is the first line of metastatic-directed local therapy for HOCRC, but its eligibility is very limited. Alternatively, RFA can be applied to patients who are ineligible for surgical resection of liver metastasis. However, there are some limitations such as inferior local control (LC) compared with surgical resection and technical feasibility based on location, size, and visibility on ultrasonography of the liver metastasis. Recent advances in radiation therapy technology have led to an increase in the use of SABR for liver tumors. SABR is considered complementary to RFA for patients with HOCRC who are ineligible for RFA. Furthermore, SABR can potentially result in better LC for liver metastases > 2-3 cm compared with RFA. In this article, the previous studies regarding curative metastasis-directed local therapies for HOCRC based on the radiation oncologist’s and surgeon’s perspective are reviewed and discussed. In addition, future perspectives regarding SABR in the treatment of HOCRC are suggested.

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Original Articles

Gastrointestinal cancer

Overview of the National Cancer Screening Program for Colorectal Cancer in Korea over 14 Years (2004-2017): Bomi Park, Eun Young Her, Kyeongmin Lee, Fatima Nari, Jae Kwan Jun, Kui Son Choi, Mina Suh; Cancer Res Treat. 2023;55(3):910-917. Published online March 8, 2023; DOI: https://doi.org/10.4143/crt.2022.1432

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study aimed to evaluate the participation and follow-up test compliance rates and key performance indicators of the National Cancer Screening Program (NCSP) for colorectal cancer (CRC) from 2004 to 2017.
Materials and Methods
The overall outcomes of the NCSP for CRC were analyzed using the NCSP data collected from 2004 to 2017 and the Korean Central Cancer Registry for CRC from 2005 to 2017. We cross-sectionally analyzed the participation and follow-up test compliance rates and performance indicators for each year. The trend of participation rates as an annual percentage change was assessed, and other statistical analyses were performed.
Results
The screening participation rates increased from 7.3% in 2004 to 30.5% in 2017. Additionally, the screening rates were higher among individuals aged 60-69 years and National Health Insurance Service beneficiaries of low-income status. However, the adherence to the follow-up test decreased from 63% in 2004 to 32% in 2017. The follow-up tests using the double-contrast barium enema method decreased from 42.2% in 2004 to 0.3% in 2017. However, follow-up tests by colonoscopy increased from 21.0% in 2004 to 31.8% in 2017. Furthermore, the positivity, false-positive, and interval CRC rates decreased, whereas the specificity increased from 2004 to 2016, indicating improved performance of CRC.
Conclusion
The participation rates and performance of the NCSP for CRC have steadily improved, whereas adherence to follow-up tests has decreased. Additionally, there is a rapid growth in colonoscopy volume as a follow-up test. Continued efforts are required to improve the follow-up rates.

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Hyoung Il Choi, Jae Myung Cha, Young Sang Kim, Dae Hyeon Cho, Han Ju Pack, Soo-Young Na, Ji Hye Kim, Hyun Gun Kim, Young-Jin Park, Hye Jung Kwon, Kyeong Ok Kim, Geon Ho Lee, Yoo Jin Lee
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Kyeongmin Lee, Mina Suh, Kui Son Choi
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Circulating Tumor DNA Dynamics and Treatment Outcome of Regorafenib in Metastatic Colorectal Cancer: Dae-Won Lee, Yoojoo Lim, Hwang-Phill Kim, Su Yeon Kim, Hanseong Roh, Jun-Kyu Kang, Kyung‑Hun Lee, Min Jung Kim, Seung-Bum Ryoo, Ji Won Park, Seung-Yong Jeong, Kyu Joo Park, Gyeong Hoon Kang, Sae-Won Han, Tae-You Kim; Cancer Res Treat. 2023;55(3):927-938. Published online March 7, 2023; DOI: https://doi.org/10.4143/crt.2023.268

Abstract PDF Supplementary Material PubReader ePub

Purpose
Circulating tumor DNA (ctDNA) is emerging as a valuable non-invasive tool to identify tumor heterogeneity and tumor burden. This study investigated ctDNA dynamics in metastatic colorectal cancer patients treated with regorafenib.
Materials and Methods
In this prospective biomarker study, plasma cell-free DNA (cfDNA) samples obtained at baseline, at the first response evaluation after 2 cycles of treatment, and at the time of progressive disease were sequenced using a targeted next-generation sequencing platform which included 106 genes.
Results
A total of 285 blood samples from 110 patients were analyzed. Higher baseline cfDNA concentration was associated with worse progression-free survival (PFS) and overall survival (OS). After 2 cycles of treatment, variant allele frequency (VAF) in the majority of ctDNA mutations decreased with a mean relative change of –31.6%. Decreases in the VAF of TP53, APC, TCF7L2, and ROS1 after 2 cycles of regorafenib were associated with longer PFS. We used the sum of VAF at each time point as a surrogate for the overall ctDNA burden. A reduction in sum (VAF) of ≥ 50% after 2 cycles was associated with longer PFS (6.1 vs. 2.7 months, p=0.002), OS (11.3 vs. 5.9 months, p=0.001), and higher disease control rate (86.3% vs. 51.1%, p < 0.001). VAF of the majority of the ctDNA mutations increased at the time of disease progression, and VAF of BRAF increased markedly.
Conclusion
Reduction in ctDNA burden as estimated by sum (VAF) could be used to predict treatment outcome of regorafenib.

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Colonoscopic Screening and Risk of All-Cause and Colorectal Cancer Mortality in Young and Older Individuals: Jung Ah Lee, Yoosoo Chang, Yejin Kim, Dong-Il Park, Soo-Kyung Park, Hye Yin Park, Jaewoo Koh, Soo-Jin Lee, Seungho Ryu; Cancer Res Treat. 2023;55(2):618-625. Published online September 19, 2022; DOI: https://doi.org/10.4143/crt.2022.852

Abstract PDF Supplementary Material PubReader ePub

Purpose
The incidence of early-onset colorectal cancer (CRC) and associated mortality have been increasing. However, the potential benefits of CRC screening are largely unknown in young individuals. We aimed to evaluate the effect of CRC screening with colonoscopy on all-cause and CRC mortality among young (aged < 45 years) and older (aged ≥ 45 years) individuals.
Materials and Methods
This cohort study included 528,046 Korean adults free of cancer at baseline who underwent a comprehensive health examination. The colonoscopic screening group was defined as those who reported undergoing colonoscopy for CRC screening. Mortality follow-up until December 31, 2019 was ascertained based on nationwide death certificate data from the Korea National Statistical Office.
Results
Colonoscopic screening was associated with a lower risk of all-cause mortality in both young and older individuals. Multivariable-adjusted time-dependent hazard ratios (95% confidence intervals) for all-cause mortality comparing ever- to never-screening were 0.86 (0.75-0.99) for young individuals and 0.71 (0.65-0.78) for older individuals. Colonoscopic screenings were also associated with a reduced risk of CRC mortality without significant interaction by age, although this association was significant only among participants aged ≥ 45 years, with corresponding time-dependent hazard ratios of 0.47 (0.15-1.44) for young individuals and 0.52 (0.31-0.87) for those aged ≥ 45 years.
Conclusion
Colonoscopic CRC screening decreased all-cause mortality among both young and older individuals, while significantly decreased CRC mortality was observed only in those aged ≥ 45 years. Screening initiation at an earlier age warrants more rigorous confirmatory studies.

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Universal Screening for Lynch Syndrome Compared with Pedigree-Based Screening: 10-Year Experience in a Tertiary Hospital: Min Hyun Kim, Duck-Woo Kim, Hye Seung Lee, Su Kyung Bang, Soo Hyun Seo, Kyung Un Park, Heung-Kwon Oh, Sung-Bum Kang; Cancer Res Treat. 2023;55(1):179-188. Published online March 21, 2022; DOI: https://doi.org/10.4143/crt.2021.1512

Abstract PDF PubReader ePub

Purpose
Universal screening for Lynch syndrome (LS) refers to routine tumor testing for microsatellite instability (MSI) among all patients with colorectal cancer (CRC). Despite its widespread adoption, real-world data on the yield is lacking in Korean population. We studied the yield of adopting universal screening for LS in comparison with pedigree-based screening in a tertiary center.
Materials and Methods
CRC patients from 2007-2018 were reviewed. Family histories were obtained and were evaluated for hereditary nonpolyposis colorectal cancer (HNPCC) using Amsterdam II criteria. Tumor testing for MSI began in 2007 and genetic testing was offered using all available clinicopathologic data. Yield of genetic testing for LS was compared for each approach and step.
Results
Of the 5,520 patients, tumor testing was performed in 4,701 patients (85.2%) and family histories were obtained from 4,241 patients (76.8%). Hereditary CRC (LS or HNPCC) was present in 69 patients (1.3%). MSI-high was present in 6.9%, and 25 patients had confirmed LS. Genetic testing was performed in 41.2% (47/114) of MSI-high patients, out of which 40.4% (19/47) were diagnosed with LS. There were six additional LS patients found outside of tumor testing. For pedigree-based screening, Amsterdam II criteria diagnosed 55 patients with HNPCC. Fifteen of these patients underwent genetic testing, and 11 (73.3%) were diagnosed with LS. Two patients without prior family history were diagnosed with LS and relied solely on tumor testing results.
Conclusion
Despite widespread adoption of routine tumor testing for MSI, this is not a fail-safe approach to screen all LS patients. Obtaining a thorough family history in combination with universal screening provides a more comprehensive ‘universal’ screening method for LS.

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Alexander T. Petterson, Jennifer Garbarini, Maria J. Baker
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Association of Body Mass Index with Survival in Asian Patients with Colorectal Cancer: Sangwon Lee, Dong Hee Lee, Jae-Hoon Lee, Su-Jin Shin, Hye Sun Lee, Eun Jung Park, Seung Hyuk Baik, Kang Young Lee, Jeonghyun Kang; Cancer Res Treat. 2022;54(3):860-872. Published online October 15, 2021; DOI: https://doi.org/10.4143/crt.2021.656

Abstract PDF Supplementary Material PubReader ePub

Purpose
The clinical significance of body mass index (BMI) on long-term outcomes has not been extensively investigated in Asian patients with colorectal cancer (CRC). This study aims to describe the association between BMI and survival, plus providing BMI cut-off value for predicting prognosis in CRC patients.
Materials and Methods
A total of 1,182 patients who had undergone surgery for stage I-III CRC from June 2004 to February 2014 were included. BMI was categorized into four groups based on the recommendation for Asian ethnicity. The optimal BMI cut-off value was determined to maximize overall survival (OS) difference.
Results
In multivariable analysis, underweight BMI was significantly associated with poor OS (hazard ratio [HR], 2.38; 95% confidence interval [CI], 1.55 to 3.71; p < 0.001) and obese BMI was associated with better OS (HR, 0.72; 95% CI, 0.53 to 0.97; p=0.036) compared with the normal BMI. Overweight and obese BMI were associated with better recurrence-free survival (HR, 0.64; 95% CI, 0.42 to 0.99; p=0.046 and HR, 0.58; 95% CI, 0.38 to 0.89; p=0.014, respectively) compared with the normal BMI group. BMI cutoff value was 20.44 kg/m². Adding the BMI cutoff value to cancer staging could increase discriminatory performance in terms of integrated area under the curve and Harrell’s concordance index.
Conclusion
Compared to normal BMI, underweight BMI was associated with poor survival whereas obese BMI was associated with better survival. BMI cut-off value of 20.44 kg/m² is a useful discriminator in Asian patients with CRC.

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Impact of overweight and obesity on gastric and colorectal cancer incidence in the older adults: a nationwide cohort study
Jinju Choi, Cheol Min Shin, Kyungdo Han, Jin-Hyung Jung, Se Yun Kim, Hyemin Jo, Ho-Kyoung Lee, Eun Hyo Jin, Seung Joo Kang, Joo Hyun Lim, Dong Ho Lee
BMC Geriatrics.2026;[Epub] CrossRef
Comment on “Dense Tumor‐Infiltrating Lymphocytes (TILs) in Liver Metastasis From Colorectal Cancer Are Related to Improved Overall Survival”
Fuji Lai, Sheng Li, Zhonglei Shen
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Body mass index, weight change, and cancer prognosis: a meta-analysis and systematic review of 73 cohort studies
H. Wen, G. Deng, X. Shi, Z. Liu, A. Lin, Q. Cheng, J. Zhang, P. Luo
ESMO Open.2024; 9(3): 102241. CrossRef
Trends in Anticoagulant Utilization and Clinical Outcomes for Cancer-Associated Thrombosis: A Multicenter Cohort Study in Thailand's Upper-Middle–Income Country Setting
Kirati Kengkla, Surakit Nathisuwan, Warunsuda Sripakdee, Pirun Saelue, Kwanruethai Sengnoo, Aumkhae Sookprasert, Suphat Subongkot
JCO Global Oncology.2024;[Epub] CrossRef
Post‐diagnosis adiposity and colorectal cancer prognosis: A Global Cancer Update Programme (CUP Global) systematic literature review and meta‐analysis
Nerea Becerra‐Tomás, Georgios Markozannes, Margarita Cariolou, Katia Balducci, Rita Vieira, Sonia Kiss, Dagfinn Aune, Darren C. Greenwood, Laure Dossus, Ellen Copson, Andrew G. Renehan, Martijn Bours, Wendy Demark‐Wahnefried, Melissa M. Hudson, Anne M. Ma
International Journal of Cancer.2024; 155(3): 400. CrossRef
Low muscle mass-to-fat ratio is an independent factor that predicts worse overall survival and complications in patients with colon cancer: a retrospective single-center cohort study
Jiabao Tang, Jingwen Xu, Xiaohua Li, Chun Cao
Annals of Surgical Treatment and Research.2024; 107(2): 68. CrossRef
Obesity, the Adipose Organ and Cancer in Humans: Association or Causation?
Elisabetta Trevellin, Silvia Bettini, Anna Pilatone, Roberto Vettor, Gabriella Milan
Biomedicines.2023; 11(5): 1319. CrossRef
Higher body mass index was associated with better prognosis in diabetic patients with stage II colorectal cancer
Xiao-Yu Liu, Bing Kang, Yu-Xi Cheng, Chao Yuan, Wei Tao, Bin Zhang, Zheng-Qiang Wei, Dong Peng
BMC Cancer.2022;[Epub] CrossRef
Preoperative carcinoembryonic antigen to body mass index ratio contributes to prognosis prediction in colorectal cancer
Jia Xiang, Mengyao Ding, Jixing Lin, Tianhui Xue, Qianwen Ye, Bing Yan
Oncology Letters.2022;[Epub] CrossRef

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A Hypoxia-Induced SCF^FBXL1 E3 Ligase Ubiquitinates and Degrades the MEN1 Tumor Suppressor to Promote Colorectal Cancer Tumorigenesis: Jun Zeng, Xiao-qing Xiao, Zhi-yong Zhou; Cancer Res Treat. 2022;54(2):525-540. Published online June 29, 2021; DOI: https://doi.org/10.4143/crt.2021.373

Abstract PDF Supplementary Material PubReader ePub

Purpose
Emerging evidence has shown that SKP1-cullin-1-F-box-protein (SCF) E3 ligases contribute to the pathogenesis of different cancers by mediating the ubiquitination and degradation of tumor suppressors. However, the functions of SCF E3 ligases in the pathogenesis of colorectal cancer (CRC) remain obscure.
Materials and Methods
The cancerous and adjacent noncancerous tissues from CRC patients were collected, and protein levels were analyzed. Lentiviral short hairpin RNA (shRNA) and plasmid transfection were used to knock down and overexpress gene expression in CRC cell lines. Immunoprecipitation (IP), mass spectrometry, and co-IP analyses were used to determine protein interactions and the assembly of the SCF complex. Cell proliferation, migration, and tumor xenograft assays were performed to examine the effects of SCF members on CRC cell growth in vitro and in vivo.
Results
Hypoxia activated the docking of hypoxia-inducible factor 1α (HIF1α) onto the CUL1 promoter and induced CUL1 expression in CRC cells. CUL1 coupled with RBX1, SKP1, and FBXL1 to assemble the SCF^FBXL1 complex in CRC biopsies and cells. The SCF^FBXL1 E3 ligase specifically ubiquitinated and degraded the MEN1 tumor suppressor. Knockdown of HIF1α or SCF^FBXL1 members, or blockage of SCF^FBXL1 by two inhibitors (DT204 and SZLP1-41) caused the accumulation of MEN1 protein and led to a significant decrease in cell proliferation and migration in vitro and tumor growth in vivo.
Conclusion
The SCF^FBXL1 E3 ligase is required for the ubiquitination of MEN1, and disruption of this complex may represent a new therapeutic strategy for the treatment of CRC.

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Targeting FOXM1 reshapes antitumor immunity to attenuate small cell lung cancer progression
Md Arafat Khan, Parvez Khan, Mahek Fatima, Asad Ur Rehman, Laiba Anwar, Zahraa Wajih Alsafwani, Aatiya Ahmad, Mohammad Ali Abbas Zaidi, Jesse L. Cox, Areem Zahid, Sameer Mohiuddin, Sung Hoon Kim, Juan A. Santamaria-Barria, Imayavaramban Lakshmanan, Benita
Cancer Letters.2026; 638: 218160. CrossRef
Long non-coding RNAs as molecular links and circulating biomarkers between type 2 diabetes and colorectal cancer: focus on shared signaling pathways, epigenetic regulation, and ubiquitination mechanisms
Lang Wu, Qing Meng, Yang Zhou
Frontiers in Molecular Biosciences.2026;[Epub] CrossRef
Role of protein degradation systems in colorectal cancer
Zihan Cui, Mingqi Cong, Shengjie Yin, Yuqi Li, Yuguang Ye, Xi Liu, Jing Tang
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Hong-Tao Liu, Si-Yuan Chen, Ling-Long Peng, Li Zhong, Li Zhou, Si-Qi Liao, Zhi-Ji Chen, Qing-Liang Wang, Song He, Zhi-Hang Zhou
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Canhui Jin, Tianbao Wang, Yanhui Yang, Pin Zhou, Juncheng Li, Wenhao Wu, Xin Lv, Guoqing Ma, Aihong Wang
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Machine Learning Model for Predicting Postoperative Survival of Patients with Colorectal Cancer: Mohamed Hosny Osman, Reham Hosny Mohamed, Hossam Mohamed Sarhan, Eun Jung Park, Seung Hyuk Baik, Kang Young Lee, Jeonghyun Kang; Cancer Res Treat. 2022;54(2):517-524. Published online June 15, 2021; DOI: https://doi.org/10.4143/crt.2021.206

Abstract PDF Supplementary Material PubReader ePub

Purpose
Machine learning (ML) is a strong candidate for making accurate predictions, as we can use large amount of data with powerful computational algorithms. We developed a ML based model to predict survival of patients with colorectal cancer (CRC) using data from two independent datasets.
Materials and Methods
A total of 364,316 and 1,572 CRC patients were included from the Surveillance, Epidemiology, and End Results (SEER) and a Korean dataset, respectively. As SEER combines data from 18 cancer registries, internal validation was done using 18-Fold-Cross-Validation then external validation was performed by testing the trained model on the Korean dataset. Performance was evaluated using area under the receiver operating characteristic curve (AUROC), sensitivity and positive predictive values.
Results
Clinicopathological characteristics were significantly different between the two datasets and the SEER showed a significant lower 5-year survival rate compared to the Korean dataset (60.1% vs. 75.3%, p < 0.001). The ML-based model using the Light gradient boosting algorithm achieved a better performance in predicting 5-year-survival compared to American Joint Committee on Cancer stage (AUROC, 0.804 vs. 0.736; p < 0.001). The most important features which influenced model performance were age, number of examined lymph nodes, and tumor size. Sensitivity and positive predictive values of predicting 5-year-survival for classes including dead or alive were reported as 68.14%, 77.51% and 49.88%, 88.1% respectively in the validation set. Survival probability can be checked using the web-based survival predictor (http://colorectalcancer.pythonanywhere.com).
Conclusion
ML-based model achieved a much better performance compared to staging in individualized estimation of survival of patients with CRC.

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International Journal of Medical Informatics.2026; 205: 106125. CrossRef
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Yongjie Zhou, Jinhong Zhao, Fei Zou, Yongming Tan, Wei Zeng, Jiahui Jiang, Jiale Hu, Qiao Zeng, Lianggeng Gong, Lan Liu, Linhua Zhong
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Gastrointestinal Cancer

Neurocognitive Effects of Chemotherapy for Colorectal Cancer: A Systematic Review and a Meta-Analysis of 11 Studies: Soo Young Hwang, Kwanghyun Kim, Byeonggwan Ha, Dongkyu Lee, Seonung Kim, Seongjun Ryu, Jisu Yang, Sun Jae Jung; Cancer Res Treat. 2021;53(4):1134-1147. Published online March 17, 2021; DOI: https://doi.org/10.4143/crt.2020.1191

Abstract PDF Supplementary Material PubReader ePub

Purpose
Chemotherapy-related cognitive impairment (CRCI) is a controversial concept not much explored on colorectal cancer patients.
Materials and Methods
We identified 11 prospective studies: eight studies on 696 colorectal cancer patients who received chemotherapy and three studies on 346 rectal cancer patients who received neoadjuvant chemoradiotherapy. Standardized mean differences (SMDs) of neuropsychological test results and the cognitive quality-of-life scale were calculated using random effect models. A meta-regression was conducted to investigate the association between mean study population age and effect sizes.
Results
The association between chemotherapy and cognitive impairment was not clear in colorectal cancer patients (SMD, 0.003; 95% confidence interval, ‒0.080 to 0.086). However, a meta-regression showed that older patients are more vulnerable to CRCI than younger patients (β=‒0.016, p < 0.001).
Conclusion
Chemotherapy has an overall positive negligible effect size on the cognitive function of colorectal patients. Age is a significant moderator of CRCI.

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Erika Cavalletto, Pamela Iannizzi, Eleonora Bergo, Daniela Grosso, Giorgia Gasparotto, Alessandra Feltrin, Nicola Galtarossa, Matteo Bernardi
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Marie‐Rose Dwek, Stanton P. Newman, Stefano Brini, Pru Holder, Michael Machesney, David Propper, Lorna R. Rixon, Shashivadan P. Hirani, Catherine S. Hurt
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Zhenzhen Su, Liyan Zhang, Xuemin Lian, Miaomiao Guan
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Neurological Complications of Conventional and Novel Anticancer Treatments
Paola Alberti, Alessandro Salvalaggio, Andreas A. Argyriou, Jordi Bruna, Andrea Visentin, Guido Cavaletti, Chiara Briani
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Effect of chemotherapy and radiotherapy on cognitive impairment in colorectal cancer: evidence from Korean National Health Insurance Database Cohort
Kwanghyun Kim, Chang Woo Kim, Aesun Shin, Hyunseok Kang, Sun Jae Jung
Epidemiology and Health.2021; 43: e2021093. CrossRef

12,685 View
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