Drug Repurposing in Gastric Cancer: Synergistic and Apoptotic Evidence of Approved Drugs with a Focus on Non-Oncologic Medications

Repurposing drugs provides a practical approach to discovering supplementary therapies in gastric cancer, especially when existing non-oncologic medications affect tumor metabolism, stress response, or resistance to cell death. This narrative review analyzes the clinical and experimental data regarding non-oncologic drugs repurposed for gastric cancer, concentrating on metformin, statins, propranolol, disulfiram-copper, proton-pump inhibitors, and particular combination approaches. In various experimental models, these agents target a restricted array of weaknesses, such as AKT-mTOR signaling, the mevalonate-RhoA-YAP/ẞ-catenin pathway, ẞ-adrenergic signaling, glycolysis, redox regulation, and proteostasis. Their impact is most credible when they reduce the threshold for chemotherapy or radiation-induced apoptosis instead of functioning as standalone cytotoxic treatments. However, the evidence is still inconsistent. Metformin possesses the most extensive preclinical record and the greatest observational literature, while simvastatin, propranolol, and disulfiram-copper are primarily backed by mechanistic studies, xenografts, or brief human biomarker trials. Increased activity in a drug combination does not equate to genuine pharmacological synergy, and numerous studies fail to assess clinically attainable drug exposure. Consequently, repurposed non-oncologic medications ought to be viewed as experimental sensitizers instead of recognized anticancer treatments. Future advancements will rely on thorough quantitative combination assessments, patient-derived models, biomarker-informed patient selection, and prospective evidence of sufficient tumor exposure and target engagement.

کلیدواژه ها:

gastric cancer ، drug repurposing ، apoptosis ، synergy ، metformin ، statins ، propranolol ، disulfiram ، non-oncologic drugs