Dual inhibition of HERs and PD-1 counteract resistance in KRAS^G12C-mutant head and neck cancer.

ABSTRACT:

Background

Basket clinical trials targeting the KRAS^G12C-mutation in solid tumors have shown initial promise, including in orphan KRAS^G12C head and neck cancer (HNC). However, development of resistance to KRAS^G12C-mutant-specific inhibitors (KRAS^G12Ci) remains a major obstacle. Here, we investigated the intrinsic (tumor-cell autonomus) and tumor-microenvironment (TME) mechanisms of resistance to the KRAS^G12Ci-MRTX849 and AMG510 in a unique syngenic murine KRAS^G12C-mutated HNC cell line.

Methods

Western-blotting was used for protein abundance and activation, overexpression, and ligand activation studies to verify the intrinsic mechanism of resistance to KRAS^G12Ci in KRAS^G12C-mutated HNC ce

SUBMITTER: Novoplansky O 

PROVIDER: S-EPMC11577641 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature