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Molecular Mechanisms and Treatment in Gastrointestinal Cancers

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Guest Editor
City of Hope National Cancer Center, Duarte, CA 91010, USA
Interests: hematology-oncology; gastrointestinal cancers; esophageal cancer

Special Issue Information

Dear Colleagues,

Gastrointestinal (GI) cancers, including malignancies of the esophagus, stomach, pancreas, liver, bile ducts, and colorectal region, remain among the leading causes of cancer-related morbidity and mortality worldwide. Recent advances in genomics, epigenetics, tumor microenvironment profiling, and immuno-oncology have deepened our understanding of the molecular underpinnings of GI cancers. These discoveries have led to the development of novel therapeutic strategies, including targeted therapies, immune checkpoint inhibitors, and combination regimens that offer hope for improved patient outcomes. This Special Issue will highlight cutting-edge research focusing on the molecular mechanisms driving GI cancer initiation, progression, metastasis, and resistance to therapy. We also seek to feature translational and clinical studies that bridge molecular insights with therapeutic innovations.

Topics of interest include (but are not limited to) the following:

  1. Molecular pathways in GI tumorigenesis and metastasis;
  2. The tumor microenvironment and immune modulation in GI cancers;
  3. Emerging biomarkers for diagnosis, prognosis, and treatment stratification;
  4. Resistance mechanisms to chemotherapy, targeted agents, and immunotherapy;
  5. Advances in liquid biopsy and molecular imaging;
  6. Preclinical models and translational approaches;
  7. Novel therapeutic combinations and clinical trial designs;
  8. The role of microbiomes and metabolism in GI tumor biology;
  9. Epigenetic regulation and gene-editing technologies.

We welcome the submission of original research articles, reviews, perspectives, and brief reports. Submissions will undergo rigorous peer review, and selected manuscripts will be published in an open-access format to ensure broad dissemination. We invite researchers, clinician-scientists, and translational investigators to contribute to this timely and impactful collection.

Dr. Dani Ran Castillo
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • gastrointestinal cancers
  • tumor microenvironment
  • immune regulation
  • biomarkers
  • therapeutic resistance
  • liquid biopsy
  • targeted therapy
  • immune checkpoint inhibitors
  • epigenetic regulation

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Further information on MDPI's Special Issue policies can be found here.

Published Papers (1 paper)

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Research

18 pages, 4782 KB  
Article
Comprehensive Analysis of SIGLEC-15 and PD-L1 Expression Identifies Distinct Prognostic Profiles in Gastric Cancer
by Andreea-Raluca Cozac-Szőke, Andreea Cătălina Tinca, Anca Negovan, Alexandra Vilaia, Dan-Alexandru Cozac, Iuliu-Gabriel Cocuz, Adrian Horațiu Sabău, Raluca-Diana Hagău, Diana-Maria Chiorean, Andreea-Bianca Lazar, Sabin Turdean, Emőke-Andrea Szász, Alexandru Nicușor Tomuț and Ovidiu Simion Cotoi
Int. J. Mol. Sci. 2025, 26(17), 8637; https://doi.org/10.3390/ijms26178637 - 5 Sep 2025
Viewed by 1088
Abstract
Gastric cancer remains a major global health burden, with limited response rates to current immunotherapies targeting the programmed death-ligand 1 (PD-1/PD-L1) axis. Recent studies have identified sialic acid-binding immunoglobulin-like lectin 15 (SIGLEC-15) as a novel immune checkpoint molecule that may drive immune evasion [...] Read more.
Gastric cancer remains a major global health burden, with limited response rates to current immunotherapies targeting the programmed death-ligand 1 (PD-1/PD-L1) axis. Recent studies have identified sialic acid-binding immunoglobulin-like lectin 15 (SIGLEC-15) as a novel immune checkpoint molecule that may drive immune evasion through PD-L1–independent pathways. This study aimed to evaluate the expression patterns of SIGLEC-15 and PD-L1 in gastric adenocarcinoma and to investigate their associations with clinicopathological features and patient outcomes. We retrospectively analyzed 133 consecutive cases of gastric adenocarcinoma with complete clinicopathologic and follow-up data. Immunohistochemical staining was performed on formalin-fixed tumor samples; SIGLEC-15 expression on tumor cells was quantified by H-score (high expression defined as ≥110) and PD-L1 status by combined positive score (CPS, positive if ≥1). High SIGLEC-15 expression correlated with multiple adverse pathological features, including lymphatic (p = 0.003), venous (p = 0.030), and perineural invasion (p = 0.010), and was associated with significantly poorer 3-year overall survival (hazard ratio = 3.36, p < 0.001). While SIGLEC-15 and PD-L1 expression were not mutually exclusive, an inverse relationship was generally observed. Patients with dual positivity (SIGLEC-15 high/PD-L1 CPS ≥ 1) showed the lowest 36-month survival (32%), compared to 56% in the dual-negative group (SIGLEC-15 low/PD-L1 CPS < 1). These results highlight the clinical relevance of SIGLEC-15 as an independent marker of tumor aggressiveness and poor prognosis in gastric adenocarcinoma. Moreover, stratification based on combined SIGLEC-15 and PD-L1 CPS expression revealed that patients co-expressing high levels of both markers experienced the poorest survival outcomes. These findings suggest that the dual assessment of SIGLEC-15 and PD-L1 may enhance prognostic accuracy and support immunotherapeutic decision-making in gastric cancer. Full article
(This article belongs to the Special Issue Molecular Mechanisms and Treatment in Gastrointestinal Cancers)
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