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Updated: Oct 9, 2025
Gene Regulation and Targeted Therapy in Gastric Cancer Peritoneal Metastasis: Radiological Findings from Dual Energy CT and PET/CT
Published on: January 22, 2018
Molecular pathogenesis, targeted therapies, and future perspectives for gastric cancer
1Section of Gastroenterology, Department of Medicine, Baylor College of Medicine, Houston, USA.
Abstract:
Gastric cancer is a major source of global cancer mortality with limited treatment options and poor patient survival. As our molecular understanding of gastric cancer improves, we are now beginning to recognize that these cancers are a heterogeneous group of diseases with incredibly unique pathogeneses and active oncogenic pathways. It is this molecular diversity and oftentimes lack of common oncogenic driver mutations that bestow the poor treatment responses that oncologists often face when treating gastric cancer. In this review, we will examine the treatments for gastric cancer including up-to-date molecularly targeted therapies and immunotherapies. We will then review the molecular subtypes of gastric cancer to highlight the diversity seen in this disease. We will then shift our discussion to basic science and gastric cancer mouse models as tools to study gastric cancer molecular heterogeneity. Furthermore, we will elaborate on a molecular process termed paligenosis and the cyclical hit model as key events during gastric cancer initiation that impart nondividing mature differentiated cells the ability to re-enter the cell cycle and accumulate disparate genomic mutations during years of chronic inflammation and injury. As our basic science understanding of gastric cancer advances, so too must our translational and clinical efforts. We will end with a discussion regarding single-cell molecular analyses and cancer organoid technologies as future translational avenues to advance our understanding of gastric cancer heterogeneity and to design precision-based gastric cancer treatments. Elucidation of interpatient and intratumor heterogeneity is the only way to advance future cancer prevention, diagnoses and treatment.
Insights
Gastric cancer is a complex disease with diverse molecular subtypes, leading to poor treatment outcomes. Understanding this heterogeneity through advanced models is key to developing precision treatments.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Gastric cancer is a leading cause of cancer mortality globally, characterized by limited therapeutic options and poor survival rates.
- The molecular diversity of gastric cancers contributes to varied pathogenetic mechanisms and treatment resistance.
- Understanding molecular heterogeneity is crucial for improving patient outcomes.
Purpose of the Study:
- To review current treatments for gastric cancer, including targeted therapies and immunotherapies.
- To explore the molecular subtypes of gastric cancer and their implications.
- To discuss basic science models and emerging technologies for studying gastric cancer heterogeneity and developing precision treatments.
Main Methods:
- Review of current literature on gastric cancer treatments, molecular subtypes, and pathogenesis.
- Discussion of gastric cancer mouse models for studying molecular heterogeneity.
- Elaboration on paligenosis and the cyclical hit model in gastric cancer initiation.
- Examination of single-cell analyses and cancer organoids for translational research.
Main Results:
- Gastric cancers exhibit significant molecular diversity, impacting treatment responses.
- Paligenosis and the cyclical hit model offer insights into gastric cancer initiation and mutation accumulation.
- Advanced technologies like single-cell analysis and organoids show promise for understanding heterogeneity.
Conclusions:
- Elucidating interpatient and intratumor heterogeneity is essential for advancing gastric cancer prevention, diagnosis, and treatment.
- Precision-based treatments require a deep understanding of molecular subtypes and individual tumor characteristics.
- Continued basic science research, coupled with translational efforts, is vital for overcoming challenges in gastric cancer therapy.
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