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Advances in Molecular Genetics and Molecular Therapy for Gastric Cancers
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Advances in Molecular Genetics and Molecular Therapy for Gastric Cancers

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 30 June 2026 | Viewed by 1333

Editor

Dr. Binnari Kim

E-Mail Website
Guest Editor
Department of Pathology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan 44610, Republic of Korea
Interests: gastric cancer; biomarker; molecular genetics; tumor microenvironment

Special Issue Information

Dear Colleagues,

Gastric cancer remains one of the leading causes of cancer-related mortality worldwide, particularly in East Asia. Recent advances in high-throughput sequencing technologies and molecular pathology have significantly expanded our understanding of the genetic and epigenetic alterations that drive gastric tumorigenesis. Key molecular features such as HER2 amplification, microsatellite instability, Epstein–Barr virus-associated gene expression, and CDH1 alterations have emerged as crucial diagnostic and therapeutic targets. Concurrently, the development of molecular-targeted therapies and immune checkpoint inhibitors has revolutionized the clinical management of gastric cancer.

This Special Issue aims to provide a comprehensive overview of the latest molecular insights and therapeutic strategies in gastric cancer, in line with the journal’s focus on molecular science. It particularly welcomes studies that bridge basic research and clinical applications.

In this Special Issue, original research articles and reviews are welcome. Topics may include, but are not limited to, the following:

  • Genomics, epigenomics, and transcriptomics in gastric cancer.
  • Biomarker discovery and validation.
  • HER2 and immune-related targets.
  • Tumor microenvironment and resistance mechanisms.
  • Novel molecular therapies and drug development.

We look forward to receiving your contributions.

Dr. Binnari Kim
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 250 words) can be sent to the Editorial Office for assessment.

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-anonymized 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

  • gastric cancer
  • molecular genetics
  • targeted therapy
  • tumor microenvironment
  • immunotherapy
  • biomarkers

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Published Papers (2 papers)

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Research

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18 pages, 2682 KB  
Article
Serum Protein Profiling of Patients at Risk to Develop Gastric Disease Based on a DSC Test
by Ombretta Repetto, Filippo Sperti, Mariangela De Zorzi, Veronica Paduano, Stefano Realdon, Agostino Steffan, Renato Cannizzaro and Valli De Re
Int. J. Mol. Sci. 2026, 27(10), 4464; https://doi.org/10.3390/ijms27104464 - 16 May 2026
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Abstract
At present, the gold standard for gastric cancer (GC) confirmation relies mostly on histopathology, an invasive procedure. Noninvasive detection methods using serum for large-scale screening may be useful for the early diagnosis of GC. Helicobacter pylori (HP) infection and chronic atrophic gastritis are [...] Read more.
At present, the gold standard for gastric cancer (GC) confirmation relies mostly on histopathology, an invasive procedure. Noninvasive detection methods using serum for large-scale screening may be useful for the early diagnosis of GC. Helicobacter pylori (HP) infection and chronic atrophic gastritis are major GC risk factors. We recently developed a noninvasive test called the DSC test-based on the patient’s age, sex, their serum PGI and PGII, anti-HP immunoglobulin (IgG), and gastrin G17 levels-predicting GC risk as low (score 0, S0) or high (score 2, S2). The comparative investigation at the serum protein level of the two different patient groups detected by our DCS test (S0 and S2) may undoubtedly help to identify gastric disease-dependent proteins, resulting from bacterial infection or gastric mucosa inflammation, as well as get better insight into the molecular scenario associated with pre-cancerous conditions. We used an untargeted liquid chromatography–tandem mass spectrometry (LC-MS/MS)-based proteomic profiling approach, followed by univariate statistical analysis to compare the different DSC groups across two patient cohorts (exploratory and validation). Significantly differentially abundant proteins differing more than 1.5-fold between S0 and S2 groups were selected and validated, and their putative role(s) in gastritis and GC were discussed. In both the exploratory and the validation cohorts, four proteins (beta-2-microglobulin, EGF-containing fibulin-like extracellular matrix protein 1, complement factor D, and cystatin-C) were more abundant, while two (sex hormone-binding globulin and pregnancy zone protein) were less abundant in the sera of S2 individuals (|fold change| ≥ 0.6, p < 0.05, t-test). The higher presence of beta-2-microglobulin (B2M) and the lower content of pregnancy zone protein (PZP) in S2 sera were validated by immunoblotting. Replacing age and sex in our DSC model with two specific candidate biomarkers can lead to a refined, albeit modest, improvement in classification accuracy. This study identified a proteomic signature that was differentially associated with the sera of patients with a different risk to develop advanced atrophy/GC according to the DSC test. Moving from a demographic model to a proteomic-driven model can better reflect the personalized biology of pathological processes associated with DSC. Full article
(This article belongs to the Special Issue Advances in Molecular Genetics and Molecular Therapy for Gastric Cancers)
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Review

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23 pages, 1099 KB  
Review
HER2-Low Gastric and Gastroesophageal Junction Adenocarcinoma: From Assessment to Treatment Strategies
by Alexandra Georgiana Scurtu, Daniela Tatiana Sala, Ioan Jung, Tivadar Bara, Radu Mircea Neagoe, Zsolt Zoltán Fülöp and Simona Gurzu
Int. J. Mol. Sci. 2026, 27(11), 4673; https://doi.org/10.3390/ijms27114673 - 22 May 2026
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Abstract
Human epidermal growth factor receptor 2 (HER2) dysregulation contributes to tumorigenesis in gastric and gastroesophageal junction adenocarcinomas (GC/GEJ). HER2 overexpression has been associated in multiple cohorts with aggressive behavior and poor outcomes. While HER2 amplification has long guided therapy in HER2-positive disease, antibody–drug [...] Read more.
Human epidermal growth factor receptor 2 (HER2) dysregulation contributes to tumorigenesis in gastric and gastroesophageal junction adenocarcinomas (GC/GEJ). HER2 overexpression has been associated in multiple cohorts with aggressive behavior and poor outcomes. While HER2 amplification has long guided therapy in HER2-positive disease, antibody–drug conjugates (ADCs) have shifted attention toward the HER2-low category, typically defined as immunohistochemistry (IHC) 1+ or IHC 2+ with negative in situ hybridization (ISH). This narrative review integrates evidence from the peer-reviewed literature, current testing recommendations, and registered clinical trials. It clarifies practical issues in HER2-low assessment and maps the evolving therapeutic landscape of HER2-targeted ADCs including rational combination strategies that may extend benefit beyond conventionally HER2-positive tumors. A cross-tumor perspective contrasts GC/GEJ testing and biology with the breast cancer paradigm and summarizes the importance of HER2-low expression in non-gastric malignancies. Finally, we discuss the therapeutic strategies in HER2-low GC/GEJ and highlight key safety and monitoring considerations for HER2-directed ADCs. Full article
(This article belongs to the Special Issue Advances in Molecular Genetics and Molecular Therapy for Gastric Cancers)
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