Perturbational Gene-Expression Signatures for Combinatorial Drug Discovery.

ABSTRACT: Cancer is a complex disease that relies on both oncogenic mutations and non-mutated genes for survival, and therefore coined as oncogene and non-oncogene addictions. The need for more effective combination therapies to overcome drug resistance in oncology has been increasingly recognized, but the identification of potentially synergistic drugs at scale remains challenging. Here we propose a gene-expression-based approach, which uses the recurrent perturbation-transcript regulatory relationships inferred from a large compendium of chemical and genetic perturbation experiments across multiple cell lines, to engender a testable hypothesis for combination therapies. These transcript-level recurrences were distinct from known compound-protein target counterparts, were reproducible in external d

SUBMITTER: Huang CT 

PROVIDER: S-EPMC6525321 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature