Pyrotinib combined with CDK4/6 inhibitor in HER2-positive metastatic gastric cancer: A promising strategy from AVATAR mouse to patients.

ABSTRACT:

Background

Pyrotinib was well tolerated but its efficacy was unsatisfactory in patients with HER2-positive gastric cancer (GC) (NCT02378389). This study was to optimize the efficacy of pyrotinib.

Methods

Human GC cell lines and AVATAR mice were used to explore the refractory mechanisms of pyrotinib. A pyrotinib-combined strategy was proposed, which was validated in preclinical AVATAR mouse and in clinical patients enrolled in a phase I clinical trial (NCT03480256).

Results

Dysregulation of CCND1-CDK4/6-Rb axis might be the key to pyrotinib refractory. The strategy of pyrotinib combined with a CDK4/6 inhibitor SHR6390 was proposed and validated in preclinical AVATAR mouse, which was successfully verified in clinical patients. For five patients treated with pyrotinib pl

SUBMITTER: Chen Z 

PROVIDER: S-EPMC7424666 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature