Precision Medicine for Gastric Cancer: Current Status and Future Directions

Abstract

Gastric cancer remains a significant global health burden, with survival rates showing limited improvement despite advances in surgery and chemotherapy. It remains one of the most challenging malignancies for researchers and clinicians, with a poor prognosis and low five-year survival rates due to chemotherapy resistance and a high tendency for metastasis. Conventional treatments have been challenged by significant tumour heterogeneity and complex molecular mechanisms. This review aims to investigate future direction and current status of precision medicine for gastric cancer. This review examined advances in precision medicine for gastric cancer, highlighting next-generation sequencing (NGS) and molecular profiling approaches that led to The Cancer Genome Atlas (TCGA) 2014 classification into four molecular subtypes: Epstein–Barr virus–positive (9% of cases), microsatellite instable (21.7%), chromosome instable (49.8%), and genome stable (19.7%). Key mutations (e.g., PIK3CA, TP53, CDH1, ARID1A), along with epigenetic alterations and deregulated non-coding RNAs, drive tumour progression and resistance to therapy. Another major challenge for targeted therapy is inter- and intratumour heterogeneity, which was extensive intratumour heterogeneity in both primary and metastatic tumours by multiregional sequencing of renal cell carcinoma. This review further discussed the impact of the tumour microenvironment and mechanisms of immune evasion, providing a rationale for emerging checkpoint inhibitors and other targeted therapies. This review uniquely integrates the mutational landscape (e.g., TP53, ARID1A mutations), epigenetic modifications, transcriptomic profiles, and tumour microenvironment to outline precise targets for next-generation personalised therapies in gastric cancer. This paper highlights the importance of integrating molecular classification and biomarker-driven treatment to advance precision care in gastric cancer. In summary, despite major breakthroughs in understanding cancer biology, the management of gastric cancer remains a challenge for both clinicians and researchers. To overcome this hurdle, newer technologies for profiling individual tumours at the molecular level and designing therapies accordingly should be adopted.