A chemical-genetic screen reveals a mechanism of resistance to PI3K inhibitors in cancer.

ABSTRACT: Linking the molecular aberrations of cancer to drug responses could guide treatment choice and identify new therapeutic applications. However, there has been no systematic approach for analyzing gene-drug interactions in human cells. Here we establish a multiplexed assay to study the cellular fitness of a panel of engineered isogenic cancer cells in response to a collection of drugs, enabling the systematic analysis of thousands of gene-drug interactions. Applying this approach to breast cancer revealed various synthetic-lethal interactions and drug-resistance mechanisms, some of which were known, thereby validating the method. NOTCH pathway activation, which occurs frequently in breast cancer, unexpectedly conferred resistance to phosphoinositide 3-kinase (PI3K) inhibitors, which are curr

SUBMITTER: Muellner MK 

PROVIDER: S-EPMC3306898 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature