DNA replication stress and mitotic catastrophe mediate sotorasib addiction in KRAS^G12C-mutant cancer.

ABSTRACT:

Background

Sotorasib is the first KRAS^G12C inhibitor approved by the US Food and Drug Administration for treating KRAS^G12C-mutant non-small-cell lung cancer (NSCLC). Clinical trials on the therapeutic use of sotorasib for cancer have reported promising results. However, KRAS^G12C-mutant cancers can acquire resistance to sotorasib after treatment. We incidentally discovered that sotorasib-resistant (SR) cancer cells are addicted to this inhibitor. In this study, we investigated the mechanisms underlying sotorasib addiction.

Methods

Sotorasib-resistant cells were established using KRAS^G12C-mutant pancreatic cancer and NSCLC cell lines. Cell viability in the presence or absence of sotorasib and in combination with multiple inhibitors w

SUBMITTER: Chiou LW 

PROVIDER: S-EPMC10308767 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature