Evaluation of KRAS^G12C inhibitor responses in novel murine KRAS^G12C lung cancer cell line models.

ABSTRACT:

Introduction

The KRAS(G12C) mutation is the most common genetic mutation in North American lung adenocarcinoma patients. Recently, direct inhibitors of the KRAS^G12C protein have been developed and demonstrate clinical response rates of 37-43%. Importantly, these agents fail to generate durable therapeutic responses with median progression-free survival of ~6.5 months.

Methods

To provide models for further preclinical improvement of these inhibitors, we generated three novel murine KRAS^G12C-driven lung cancer cell lines. The co-occurring NRAS^Q61L mutation in KRAS^G12C-positive LLC cells was deleted and the KRAS^G12V allele in CMT167 cells was edited to KRAS^G12C with CRISPR/Cas9 methods. Also, a novel murine KRAS<

SUBMITTER: Sisler DJ 

PROVIDER: S-EPMC9945252 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature