Combined HASPIN and mTOR inhibition is synergistic against KRAS-driven carcinomas.

ABSTRACT:

Background

Oncogenic mutations in the KRAS gene are very common in human cancers, resulting in cells with well-characterized selective advantages. For more than three decades, the development of effective therapeutics to inhibit KRAS-driven tumorigenesis has proved a formidable challenge and KRAS was considered 'undruggable'. Therefore, multi-targeted therapy may provide a reasonable strategy for the effective treatment of KRAS-driven cancers. Here, we assess the efficacy and mechanistic rationale for combining HASPIN and mTOR inhibition as a potential therapy for cancers carrying KRAS mutations.

Methods

We investigated the synergistic effect of a combination of mTOR and HASPIN inhibitors on cell viability, cell cycle, cell apoptosis, DNA damage, and mitotic catastrophe usin

SUBMITTER: Xu C 

PROVIDER: S-EPMC9483799 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature