Advancing Gastric Cancer Chemoprevention: Early Signals and Ongoing Challenges.

Chemoprevention for gastric cancer remains underdeveloped despite a well-defined premalignant window and a substantial burden in high-risk populations. Two phase IIa trials conducted in Puerto Rico and Honduras evaluated curcuminoids and eflornithine in patients with gastric premalignant conditions. Curcuminoids reduced IL1β, whereas eflornithine showed a possible delayed reduction in pH2AX-defined DNA damage. Both agents were generally well tolerated, although hearing-related adverse events were more frequent in eflornithine. Together, these studies support the feasibility of mechanism-based chemoprevention for gastric cancer while highlighting key challenges in patient selection, surrogate endpoint validation, long-term safety, and, critically, the demonstration of durable cancer prevention beyond short-term biomarker modulation. See related article by Morgan et al., p. 391 See related article by Gonzalez-Pons et al., p. 403.