CDK7 inhibition for drug-resistant cancers

DISEASE CATEGORY: Cancer

Inhibiting CDK7 could treat hedgehog signaling-driven cancers resistant to SMO inhibitors. A CDK7 inhibitor tool compound decreased viability of cells resistant to SMO inhibitors and driven by activating mutations in the hedgehog signaling pathway, in assays on human medulloblastoma, Ewing sarcoma and atypical teratoid rhabdoid cell lines. In the Ewing sarcoma and atypical teratoid rhabdoid cell lines, the CDK7 inhibitor CT7001 decreased viability with IC₅₀ values of 0.33 µM and 0.82 µM, respectively. Knockout of CDK7 in tumors or the CDK7 inhibitor decreased tumor growth in a mouse model of SMO inhibitor-resistant hedgehog-driven medulloblastoma; the inhibitor also extended mouse survival. ...