Multi-targeted kinase inhibition alleviates mTOR inhibitor resistance in triple-negative breast cancer.

ABSTRACT:

Purpose

Owing to its genetic heterogeneity and acquired resistance, triple-negative breast cancer (TNBC) is not responsive to single-targeted therapy, causing disproportional cancer-related death worldwide. Combined targeted therapy strategies to block interactive oncogenic signaling networks are being explored for effective treatment of the refractory TNBC subtype.

Methods

A broad kinase inhibitor screen was applied to profile the proliferative responses of TNBC cells, revealing resistance of TNBC cells to inhibition of the mammalian target of rapamycin (mTOR). A systematic drug combination screen was subsequently performed to identify that AEE788, an inhibitor targeting multiple receptor tyrosine kinases (RTKs) EGFR/HER2 and VEGFR, synergizes with selective mTOR inhibitor

SUBMITTER: He J 

PROVIDER: S-EPMC6797661 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature