Chromatin accessibility trajectories reveal pre-cancerous epigenetic priming and an acid-driven immunotherapy-resistant gastric cancer subtype.

Chromatin accessibility changes reveal a pre-cancerous epigenetic priming and identify an acid-driven, immunotherapy-resistant gastric cancer subtype with a 650-sample atlas.

• Why it matters: Understanding how chromatin dynamics influence tumor development can improve early detection and treatment strategies, especially for resistant cancer subtypes.
• What they did: Decoding chromatin accessibility in 650 samples from 439 patients uncovered epigenetic switches during gastric tumorigenesis and classified tumors into three subtypes, including a resistant pseudo-gastric type driven by FOSL2.
• The result: Targeting the acid-producing phenotype with FOSL2 depletion or vonoprazan sensitizes tumors to immunotherapy, offering a potential approach to overcome drug resistance and improve patient outcomes.