Dependence of NPPS creates a targetable vulnerability in RAS-mutant cancers.

ABSTRACT: RAS is the most frequently mutated oncoprotein for cancer driving. Understanding of RAS biology and discovery of druggable lynchpins in RAS pathway is a prerequisite for targeted therapy of RAS-mutant cancers. The recent identification of KRAS^G12C inhibitor breaks the "undruggable" curse on RAS and has changed the therapy paradigm of KRAS-mutant cancers. However, KRAS mutations, let alone KRAS^G12C mutation, account for only part of RAS-mutated cancers. Targeted therapies for cancers harboring other RAS mutations remain the urgent need. In this study we explored the pivotal regulatory molecules that allow for broad inhibition of RAS mutants. By comparing the expression levels of nucleotide pyrophosphatase (NPPS) in a panel of cell lines and the functional consequence o

SUBMITTER: Xia RX 

PROVIDER: S-EPMC11845791 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature