NIH R01 · 2025
Overcoming adaptive feedback resistance to KRAS inhibition in colorectal cancer
Project Summary/Abstract Although KRAS is mutated in 20% of all cancers and 40% of colorectal cancer (CRC), it has long been considered an “undruggable” target 1. Recently, novel covalent inhibitors selective for KRASG12C have entered the clinic, offering the unprecedented opportunity to target KRAS directly, and other mutation-specific KRAS inhibitors (i.e. G12D) are under development 2,3. However, prior efforts to target the RAS-MAPK pathway have been hampered by adaptive feedback, which drives pathway reactivation and resistance, particularly in CRC. For example, BRAF inhibition in BRAFV600 CRC leads to loss of ERK-dependent negative feedback and RTK- mediated pathway reactivation,…
From the public funding record at NIH RePORTER. Describes the funded project, not the reviews below.