PIK3CA hotspot mutations differentially impact responses to MET targeting in MET-driven and non-driven preclinical cancer models.

ABSTRACT:

Background

The MET receptor tyrosine kinase represents a promising target in cancer. PIK3CA activating mutations are common in several tumor types and can potentially confer resistance to anti-receptor tyrosine kinase therapy.

Methods

MET and/or PI3K pathway inhibition was assessed in NIH3T3 cells harboring MET-activating point mutation with or without ectopic expression of PIK3CA^E545K and PIK3CA^H1047R, as well as in MET-expressing head and neck cancer cells with endogenous PIK3CA mutations. Endpoints included PI3K pathway activation, cell proliferation, colony-forming ability, cell death, wound-healing, and an in vivo model.

Results

PIK3CA^E545K and PIK3CA^H1047R confer resistance to MET inhibition in MET-driven models. PIK3C

SUBMITTER: Nisa L 

PROVIDER: S-EPMC5441085 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature