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

PP01.24 Choi - Poster

Pdf Summary

The document discusses the investigation of a new pan-RAS inhibitor, RMC-7797, for KRAS-mutant non-small cell lung cancer and colorectal cancer. The study highlights the sensitivity of different tumor models to the inhibitor and its correlation with the PI3K/AKT/mTOR pathway inhibition. It identifies lineage-specific differences in PI3K/AKT/mTOR signaling networks between NSCLC and CRC. The findings suggest that mTORC1 dependency is a therapeutic vulnerability for KRAS-mutant NSCLC, with mTORC1 inhibition leading to tumor regression in NSCLC models. However, CRC tumors respond better to combination treatment with an AKT inhibitor than mTORC1 inhibition due to AKT-independent mTORC1 signaling. The study emphasizes the importance of understanding the signaling biology for effective targeting of tumors. Additionally, it demonstrates the synergistic effect of combining KRAS inhibition with mTORC1-selective inhibition in NSCLC mouse models. The document also includes details of cell line experiments, dose-response curves, and resistance index scores, shedding light on the effects of RMC-7797 on different cancer cell lines. Ultimately, the findings underscore the significance of mTORC1 activity and the potential of combination therapies for treating KRAS-mutant cancers.

Keywords

pan-RAS inhibitor

RMC-7797

KRAS-mutant

non-small cell lung cancer

colorectal cancer

PI3K/AKT/mTOR pathway

mTORC1 inhibition

combination treatment

signaling networks

tumor regression