LSD1 is a targetable vulnerability in gastric cancer harboring TP53 frameshift mutations.

ABSTRACT:

Background

TP53 mutations are linked to aggressive progression and chemoresistance in gastric cancer (GC). Frameshift mutation is the second most common mutation type of TP53. However, the consequences of this mutation type in GC were not well understood, and targeted therapies for cancer patients harboring frameshift mutations were also not established. Histone methylation significantly influences tumorigenesis in TP53-mutated cancers, and related inhibitors are emerging as specific therapeutic strategies.

Methods and results

By treating GC cell lines harboring various TP53 mutation types with a library of histone demethylase inhibitors, we identified that GSK690, a reversible inhibitor of lysine-specific demethylase 1 (LSD1), selectively inhibits GC cells harboring TP53 fr

SUBMITTER: Wang S 

PROVIDER: S-EPMC11837680 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature