Computational repurposing of approved drugs targeting KRAS G12D and EGFR for colorectal cancer therapy.

ABSTRACT:

Background/objectives

Colorectal cancer is characterized by various oncogenic mutations, with the KRAS G12D mutation being the most prevalent. The development of MRTX1133 has revitalized the KRAS direct targeting. However, colorectal cancer demonstrated intrinsic resistance to MRTX1133, primarily due to the feedback activation of the EGFR pathway. Combining KRAS G12D and EGFR inhibition has demonstrated improved treatment efficacy, highlighting the potential of dual-targeting approaches in colorectal cancer therapy. This study employs CADD tools to identify approved drugs capable of dual targeting KRAS G12D and EGFR.

Methods

A library of 3,591 approved drugs was screened against KRAS G12D using high-throughput virtual screening (HTVs), standard precision (SP) and extra preci

SUBMITTER: Ibraheem W 

PROVIDER: S-EPMC12851494 | biostudies-literature | 2026

REPOSITORIES: biostudies-literature