Loss of MAP3K7 Sensitizes Prostate Cancer Cells to CDK1/2 Inhibition and DNA Damage by Disrupting Homologous Recombination.

ABSTRACT: The combined loss of CHD1 and MAP3K7 promotes aggressive prostate cancer by unknown mechanisms. Because both of these genes are lost genetically in prostate cancer, they cannot be directly targeted. We applied an established computational systems pharmacology approach (TRAP) to identify altered signaling pathways and associated druggable targets. We compared gene expression profiles of prostate cancer with coloss of CHD1 and MAP3K7 with prostate cancer diploid for these genes using The Cancer Genome Atlas patient samples. This analysis prioritized druggable target genes that included CDK1 and CDK2. We validated that inhibitors of these druggable target genes, including the CDK1/CDK2 inhibitor dinaciclib, had antiproliferative and cyto

SUBMITTER: Washino S 

PROVIDER: S-EPMC7266379 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature