Combined inhibition of CDK12 and CDK13 for TNBC

INDICATION: Breast cancer

A Moffitt Cancer Center and Research Institute team showed that dual inhibition of CDK12 and CDK13 could treat triple-negative breast cancer (TNBC). In four human TNBC cell lines, an optimized heteroaromatic purine based on a CDK12 and CDK13 inhibitor tool compound inhibited proliferation with EC₅₀ values of 15.5-24.9 nM. In three of the lines, the optimized compound plus generic chemotherapies cisplatin, doxorubicin and irinotecan or Lynparza olaparib synergistically decreased proliferation. In patient-derived xenograft (PDX) mouse models of TNBC, the compound plus cisplatin or irinotecan reduced tumor growth, with the irinotecan combination eliminating detectable disease in half the mice...