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Gastrointestinal Cancers: From Pathogenesis to Treatment

A special issue of Current Issues in Molecular Biology (ISSN 1467-3045). This special issue belongs to the section "Molecular Medicine".

Deadline for manuscript submissions: 30 November 2026 | Viewed by 2719

Special Issue Editors


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Guest Editor
1. Department of Medical Research, E-Da Cancer Hospital, Kaohsiung, Taiwan
2. Department of Nursing, College of Medicine, I-Shou University, Kaohsiung, Taiwan
Interests: tumor microenvironment; GRP78; extracellular vesicles; mitochondria; gastric cancer; breast cancer; cancer stemness
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Special Issue Information

Dear Colleagues,

Gastric cancer remains one of the most lethal malignancies worldwide, continuing to pose a major challenge in clinical oncology. Despite advances in diagnosis and therapy, the prognosis for patients with advanced or recurrent gastric cancer remains poor. Systemic multidrug chemotherapy is widely applied as a standard treatment; however, its efficacy is often hampered by tumor heterogeneity and the frequent emergence of chemoresistance.

Accumulating evidence highlights the pivotal role of gastric cancer stem cells (CSCs) in mediating chemoresistance, tumor relapse, and metastasis. CSCs possess unique capabilities for self-renewal, differentiation, and tumor initiation, enabling them to survive conventional treatments and repopulate tumors. Among the key regulatory pathways, nuclear factor erythroid 2-related factor 2 (Nrf2) has emerged as a crucial transcription factor maintaining cellular redox balance by regulating antioxidant enzyme expression. Enhanced Nrf2 activity within CSCs contributes to their resistance to oxidative stress and therapy-induced cytotoxicity. Nrf2-mediated extracellular vesicles (EVs) also play a pivotal role in facilitating communication between CSCs and tumor microenvironment cells.

The interplay between CSCs and antioxidant transcriptional networks, such as Nrf2 signaling, represents a novel conceptual framework for understanding gastric cancer progression and therapeutic resistance. Exploring this crosstalk could unveil innovative strategies for targeting redox homeostasis and stemness in gastric tumors. Furthermore, increasing evidence suggests that nutritional or natural compounds capable of modulating antioxidant pathways and CSC activity may offer promising preventive or therapeutic benefits in gastrointestinal cancers.

In line with these emerging insights, this Special Issue welcomes original research articles, reviews, and communications focusing on novel treatment strategies, molecular mechanisms of chemoresistance, and the pathogenesis of gastrointestinal cancers. Studies exploring the biological regulation of CSCs, redox signaling, EVs-gastric cancer cell communication and the therapeutic potential of natural compounds are particularly encouraged.

Dr. Mingwei Lin
Dr. Cheng-Che Lee
Guest Editors

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Keywords

  • gastric cancer
  • cancer stem cells (CSCs)
  • Nrf2 signaling
  • chemoresistance
  • extracellular vesicles (EVs)
  • redox homeostasis

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Published Papers (3 papers)

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Research

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11 pages, 773 KB  
Article
Quantification of the Human Satellite 2 (HSAT2) Repeat in the Plasma Cell-Free DNA of Patients with Colon Cancer
by Ebru Esin Yörüker, Emre Özgür, Cemil Burak Kulle, Betül Aksu, Ilgin Gökçe Demir, Abel Bronkhorst, Stefan Holdenrieder and Ugur Gezer
Curr. Issues Mol. Biol. 2026, 48(3), 256; https://doi.org/10.3390/cimb48030256 - 27 Feb 2026
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Abstract
Background/Objectives: Liquid profiling of molecular and epigenetic markers in bodily fluids is an expanding field of cancer biomarker research. Recent research activity also reveals the human satellite 2 (HSAT2) repetitive element cell-free DNA (cfDNA) as a potential cancer biomarker. Based on our recent [...] Read more.
Background/Objectives: Liquid profiling of molecular and epigenetic markers in bodily fluids is an expanding field of cancer biomarker research. Recent research activity also reveals the human satellite 2 (HSAT2) repetitive element cell-free DNA (cfDNA) as a potential cancer biomarker. Based on our recent results from targeted sequencing of HSAT2 cfDNA, we tested whether a specific HSAT2 sequence (e.g., 95 bp-HSAT2) shows greater cancer enrichment than 114 bp-SAT2, from which it derives, in patients with colon cancer. Methods: By comparing the ratio of 114 bp-HSAT2 to 95 bp-HSAT2, we investigated the increased cancer enrichment of 95 bp-HSAT2 in cfDNA samples obtained from plasma DNA extraction and a hybridization capture assay, in which HSAT2 sequences were captured from plasma using a biotin-labeled probe, in samples from colon cancer patients (n = 60) and polyp-controls (n = 60), and polyp-free controls (n = 60). Results: A correlation analysis between Ct values from DNA extraction and the hybridization capture assay for both 95 bp- and 114 bp-HSAT2 showed a positive correlation in patients with colon cancer and control subjects, indicating that the hybridization capture assay provides HSAT2 levels comparable to those obtained by DNA extraction. With both approaches, we found a lower 114 bp-HSAT2 to 95 bp-HSAT2 ratio in patients with colon cancer than in the control groups. The median ratio of extracted DNA was 62, 78, and 79 in patients with colon cancer, polyp-controls (p = 0.23), and polyp-free controls (p = 0.067), respectively. Capture assay values were 49, 87, and 64 in patients with colon cancer, polyp controls (p = 0.016), and polyp-free controls (p = 0.19), respectively. Even though statistical significance was not achieved in some comparisons, these results suggest that 95 bp-HSAT2 is more abundant in the blood of patients with colon cancer than 114 bp-HSAT2 in non-malignant patients. Conclusions: To our knowledge, this is the first study to conduct a hybridization capture assay using a biotinylated probe as a feasible approach for targeted enrichment of cfDNA from plasma. Our results confirm the outcomes of our recent article based on targeted sequencing and reveal that some specific HSAT2 sequences may exhibit increased cancer abundance. Full article
(This article belongs to the Special Issue Gastrointestinal Cancers: From Pathogenesis to Treatment)
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16 pages, 2938 KB  
Article
Integrative Bioinformatics and Experimental Validation Establish CCNB1 as a Potential Biomarker for Diagnosis and Prognosis in Colorectal Cancer
by Yao Zou, Quan Zou and Zhen Li
Curr. Issues Mol. Biol. 2025, 47(12), 1026; https://doi.org/10.3390/cimb47121026 - 9 Dec 2025
Viewed by 835
Abstract
Colorectal cancer (CRC) is a prevalent and lethal malignancy worldwide. Despite extensive research, core genes for diagnosis and prognosis in CRC remain to be fully elucidated. This study aims to identify novel gene biomarkers for CRC diagnosis and prognosis based on the GEO [...] Read more.
Colorectal cancer (CRC) is a prevalent and lethal malignancy worldwide. Despite extensive research, core genes for diagnosis and prognosis in CRC remain to be fully elucidated. This study aims to identify novel gene biomarkers for CRC diagnosis and prognosis based on the GEO and TCGA datasets. Integration of TCGA and GEO datasets revealed 197 common differentially expressed genes (DEGs) between CRC tumor and normal samples. Functional enrichment analysis implicated these DEGs in biological processes and signaling pathways critical to CRC progression, including cell cycle regulation and nuclear division. Protein–protein interaction (PPI) network analysis identified 17 hub genes from DEGs, including TROAP, CDKN3, CDCA3, UBE2C, CEP55, KIF11, CDC20, CCNA2, MCM4, CKS2, POLE2, MAD2L1, CCNB1, PTTG1, TPX2, TOP2A, and DLGAP5. All 17 hub genes demonstrated high diagnostic value (AUC > 0.85), including CCNB1 (AUC = 0.944). Based on the Cox proportional hazards regression, an 8-gene prognostic signature (CLCA1, CCNB1, TPM2, MMP3, AOC3, CRYAB, CA4, GUCA2A) effectively stratified patients by survival risk, with a 5-year AUC of 0.71. In vitro, CCNB1 knockdown triggered cell cycle arrest, thereby suppressing the proliferation of colorectal cancer cells. This study validated CCNB1 as a dual-purpose biomarker for CRC diagnosis and favorable prognosis, highlighting its potential utility in clinical management. Full article
(This article belongs to the Special Issue Gastrointestinal Cancers: From Pathogenesis to Treatment)
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Review

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18 pages, 817 KB  
Review
Antibody-Mediated Therapy in Gastric Cancer: Past, Present, and Future
by Hong-Beum Kim and Sang-Gon Park
Curr. Issues Mol. Biol. 2025, 47(12), 1044; https://doi.org/10.3390/cimb47121044 - 15 Dec 2025
Cited by 1 | Viewed by 1283
Abstract
The limited efficacy of cytotoxic chemotherapy in the context of gastric cancer treatment is largely driven by profound molecular and biological heterogeneity. In contrast, the development of antibody-mediated therapies has ushered in a new era of precision oncology by enabling selective molecular targeting [...] Read more.
The limited efficacy of cytotoxic chemotherapy in the context of gastric cancer treatment is largely driven by profound molecular and biological heterogeneity. In contrast, the development of antibody-mediated therapies has ushered in a new era of precision oncology by enabling selective molecular targeting and immune modulation. This review includes a comprehensive overview of the evolution of antibody-based therapeutics in gastric cancer, highlighting early breakthroughs, subsequent setbacks, and recent advances that have reshaped the treatment landscape. We summarize the current standard regimens targeting HER2, VEGFR2, PD-1/PD-L1, and CLDN18.2 and examine pivotal clinical trials evaluating monoclonal antibodies directed against these pathways. We also discuss emerging therapeutic modalities, including next-generation antibody–drug conjugates (ADCs), bispecific antibodies, and chimeric antigen receptor (CAR) T-cell therapies. Trastuzumab first established HER2-targeted therapy in gastric cancer, but the failure of trastuzumab emtansine (T-DM1) led to a decade-long stagnation until the advent of trastuzumab deruxtecan (T-DXd), which demonstrated robust clinical activity and defined a new standard of care. While bevacizumab failed to improve survival, the anti-VEGFR2 antibody ramucirumab emerged as an effective second-line therapy. Immune checkpoint inhibitors, including nivolumab and pembrolizumab, have been incorporated into first-line treatment for PD-L1-positive disease based on landmark trials such as CheckMate 649 and KEYNOTE-811. More recently, the CLDN18.2-targeted antibody zolbetuximab has expanded therapeutic options for biomarker-selected patients. Concurrently, a diverse pipeline of immune-based strategies—such as TROP2-directed ADCs, bispecific antibodies, and CAR-T cell therapies—is undergoing active clinical development. Together, advances in biomarker-driven antibody therapeutics are accelerating personalized cancer care and improving clinical outcomes in patients with gastric cancer. Full article
(This article belongs to the Special Issue Gastrointestinal Cancers: From Pathogenesis to Treatment)
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