PI3K/AKT/mTOR pathway inhibitors inhibit the growth of melanoma cells with mTOR H2189Y mutations in vitro.

ABSTRACT: mTOR is an important therapeutic target in many types of cancers. In melanoma, the mTOR nonsynonymous mutation rate is up to 10.4%. However, mTOR inhibitors have shown limited effects in clinical trials of melanoma. Because mTOR mutations are distributed, not selecting patients with specific mTOR mutations may be the main reason for therapeutic failures. Our previous research found that mutations in the mTOR P2213S and S2215Y kinase domains resulted in gain-of-function and were sensitive to specific inhibitors. The purpose of this study was to test the effect of heterozygous/homozygous H2189Y mutations on downstream pathways and sensitivity to inhibitors. mTOR kinase activity was analyzed by western blot and a K-LISA™ mTOR activity kit. The sensitivity of melanoma cells to inhibitors was t

SUBMITTER: Wu X 

PROVIDER: S-EPMC5989792 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature