Targeting PRMT1 Reduces Cancer Persistence and Tumor Relapse in EGFR- and KRAS-Mutant Lung Cancer.

ABSTRACT:

Abstract

Incomplete killing of cancer cells undermines oncogene-targeting therapies and drives disease relapse. Eliminating cancer cells that persist during treatment is crucial for improving treatment outcomes. Here, we discovered that a specific isoform of type I protein arginine methyltransferases (PRMT), namely, PRMT1, enables lung cancer cells with EGFR or KRASG12C driver mutations and high STAT1 activity to persist through targeted drug treatments. PRMT1 knockdown, combined with EGFR or KRASG12C inhibitors, decreased persistence and delayed cancer cell regrowth across cell line models and significantly prolonged tumor regression in xenograft models. In contrast, we found that knockdown of two other type I PRMT isoforms, PRMT4 and PRMT6, increased persistence. Finally, we foun

SUBMITTER: Sun X 

PROVIDER: S-EPMC11747858 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature