Inhibiting CDK14 for TNBC

Inhibiting CDK14, a kinase regulator of cell proliferation and migration, could help treat triple negative breast cancer (TNBC) by regulating mammary stem cell activity and metastasis. In a patient-derived xenograft mouse model of TNBC, RNAi knockdown of CDK14 decreased tumor volume and weight, and increased the percentage of tumor-free mice compared with scrambled RNAi. In a patient-derived xenograft mouse model of TNBC metastasis, knockdown of CDK14 decreased metastasis and increased survival compared with normal expression. Also in the two models, a CDK14 inhibitor tool compound decreased tumor growth and lung metastases, respectively, compared with the CDK4/6 inhibitor Verzenio abemaciclib. In a patient-derived organoid model of TNBC, the CDK14 inhibitor increased tumor cell apoptosis and decreased organoid proliferation compared with vehicle.

Eli Lilly and Co. (NYSE:LLY) markets Verzenio for breast cancer, and has the compound in Phase III and Phase II testing for other cancers...