KRAS-Driven Hypertranscription and Metastatic Dissemination in Colorectal Cancer Could be Overcome by Targeting the NMHC IIA/ PLK1 Signaling Axis with a Novel Acridine Derivative.

ABSTRACT: Colorectal cancer (CRC) becomes highly lethal upon progression to advanced or metastatic stages. Treatment options are particularly limited for refractory metastatic CRC (mCRC) harboring KRAS mutations. In this study, we established a series of patient-derived organoids (PDOs) and patient-derived xenografts (PDXs) from mCRC patients to identify effective therapeutic compounds. We employed RNA sequencing to characterize the transcriptomic profiles of KRAS-mutant microsatellite stable (MSS) PDOs and analyzed single-cell RNA sequencing data to examine features of KRAS-mutant CRC epithelial cells. Transcriptomic analysis revealed that KRAS mutations induce elevated global transcription activity in both PDOs and epithelial cells. A large-scale drug screen of 786 Food and Drug Administration (FD

SUBMITTER: Ji D 

PROVIDER: S-EPMC12681934 | biostudies-literature | 2026

REPOSITORIES: biostudies-literature