MEK inhibition overcomes resistance to EphA2-targeted therapy in uterine cancer.

ABSTRACT:

Background

Our pilot clinical study of EphA2 inhibitor (dasatinib) plus paclitaxel and carboplatin showed interesting clinical activity in endometrial cancer with manageable toxicity. However, the underlying mechanisms of dasatinib resistance in uterine cancer are unknown. Here, we investigated potential mechanisms underlying resistance to EphA2 inhibitors in uterine cancer and examined the anti-tumor activity of EphA2 inhibitors alone and in combination with a MEK inhibitor.

Methods

We evaluated the antitumor activity of EphA2 inhibitors plus a MEK inhibitor using in vitro and in vivo orthotopic models of uterine cancer.

Results

EphA2 inhibitor induced MAPK in dasatinib-resistant uterine cancer cells (HEC-1A and Ishikawa) and BRAF/CRAF heterodimerization in HEC-1A ce

SUBMITTER: Wu Y 

PROVIDER: S-EPMC8511168 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature