A Combination CDK4/6 and IGF1R Inhibitor Strategy for Ewing Sarcoma.

ABSTRACT:

Purpose

Novel targeted therapeutics have transformed the care of subsets of patients with cancer. In pediatric malignancies, however, with simple tumor genomes and infrequent targetable mutations, there have been few new FDA-approved targeted drugs. The cyclin-dependent kinase (CDK)4/6 pathway recently emerged as a dependency in Ewing sarcoma. Given the heightened efficacy of this class with targeted drug combinations in other cancers, as well as the propensity of resistance to emerge with single agents, we aimed to identify genes mediating resistance to CDK4/6 inhibitors and biologically relevant combinations for use with CDK4/6 inhibitors in Ewing.

Experimental design

We performed a genome-scale open reading frame (ORF) screen in 2 Ewing cell lines sensitive to CDK4/6 inhi

SUBMITTER: Guenther LM 

PROVIDER: S-EPMC6498855 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature