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Gastric Signet Ring Cell Carcinoma: Tumor Microenvironment Reprogramming and Novel Therapeutic Targets With Emphasis
Dipali Raju1, Swathi Prabhu2, Anjal Maria3
1Department of Surgical Oncology, Manipal Comprehensive Cancer Care Center, Kasturba Medical College, Manipal Academy of Higher Education, Manipal, Karnataka, India.
Clinical and Translational Science
|November 18, 2025
Summary
Gastric Signet Ring Cell Carcinoma (GSRCC) is an aggressive cancer subtype, common in South Asia. Understanding its unique tumor microenvironment and biomarkers like GRIN2D is key to developing new treatments.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Gastric Signet Ring Cell Carcinoma (GSRCC) is an aggressive gastric cancer subtype with poor prognosis, prevalent in South Asian populations.
- GSRCC is characterized by mucinous cells, early onset, advanced stage at diagnosis, and resistance to conventional therapies.
- The tumor microenvironment in GSRCC is immunosuppressive and stroma-rich, featuring immune dysfunction, activated fibroblasts, and complement system anomalies.
Purpose of the Study:
- To review the unique characteristics of GSRCC, focusing on its tumor microenvironment and key biomarkers.
- To explore the mechanisms of therapeutic resistance and immune evasion in GSRCC.
- To identify novel therapeutic strategies for improving patient outcomes in GSRCC.
Main Methods:
- Literature review of recent research on GSRCC pathogenesis, biomarkers, and therapeutic resistance.
- Analysis of the role of the tumor microenvironment, including immune cells and stromal components.
- Identification and discussion of emerging biomarkers such as MSMB, AGR2, CLDN18.2, and GRIN2D.
Main Results:
- GSRCC exhibits a distinct immunosuppressive microenvironment contributing to treatment resistance.
- Biomarkers including GRIN2D are implicated in tumor angiogenesis, immune evasion, and metabolic reprogramming.
- Therapeutic resistance is linked to the interplay between tumor cells, stroma, and immune components.
Conclusions:
- Targeting the stromal-rich microenvironment and specific biomarkers like GRIN2D offers promising therapeutic avenues for GSRCC.
- Innovative strategies involving stromal-targeting agents, complement modulators, and anti-CLDN18.2 therapies are under investigation.
- Personalized management through early detection and biomarker monitoring is crucial for transforming GSRCC treatment.
Keywords:
GRIN2DGastric Signet Ring Cell Carcinomaimmune evasiontherapy resistancetumor microenvironmentMore Related Videos
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