2024 Targeted Therapies for Lung Cancer (TTLC) - Abstracts & Posters-PP01.24 Choi

PP01.24 Choi - Abstract

Pdf Summary

In a study by Kitai et al., the combination of inhibiting KRASG12C and mTORC1 kinase in non-small cell lung cancer (NSCLC) has been shown to cause synergistic cell death and tumor regression in preclinical models. KRAS mutations are common in NSCLC, with KRASG12C being a prevalent variant. Current inhibitors targeting the inactive state of KRASG12C have shown some efficacy in clinical trials, but resistance mechanisms often emerge, necessitating more potent inhibitors or combination therapies. The study evaluated an active-state KRASG12C inhibitor (RM-018) in combination with PI3K/mTOR pathway inhibitors, demonstrating enhanced efficacy in both cell line and mouse models. The combination treatment led to potent inhibition of cell growth and induction of apoptosis by targeting multiple key signaling pathways. The results suggest that inhibiting PI3K/mTOR is crucial for sensitivity to KRASG12C inhibitors in NSCLC. The study highlights the potential of this combination therapy for treating KRASG12C mutant-driven NSCLC and supports the need for further clinical evaluation of this approach.

Keywords

KRASG12C

mTORC1 kinase

non-small cell lung cancer

tumor regression

KRAS mutations

cell death

combination therapy

PI3K/mTOR pathway inhibitors

apoptosis

clinical evaluation