Dr. Hasem Habelhah received a five-year NIH R01 entitled ‘The Roles of TRAF2 and RIP1 in Breast Cancer Cell Survival’ from the National Cancer Institute (NCI).

Breast cancer is the most frequently diagnosed malignancy and the second leading cause of cancer mortality in western women. In about 80% of breast cancer cases, the PI3K-AKT pathway is aberrantly activated, and over 100 clinical trials have been conducted worldwide to evaluate the therapeutic efficacy of PI3K and AKT inhibitors in breast cancer; however, the data reported so far revealed that inhibition of this pathway is either not effective or often results in development of resistance and relapse of the disease. This project will investigate the signaling cross-talk between the PI3K-AKT and TBK1-TRAF2-RIP1 pathways, and evaluate the therapeutic efficacies of combined inhibition of AKT and TBK1 in patient-derived xenograft (PDX) tumor models of breast cancer. This project builds upon previous findings that inhibition of the PI3K-AKT pathway leads to increased activation of the TBK1-TRAF2-RIP1 pathway in breast cancer cells, and that inhibition of TBK1 significantly sensitizes breast cancer cells to AKT inhibition. TBK1 and its close homologous IKKi are oncogenic kinases that promote breast cancer cell survival. The research will be conducted in collaboration with Dr. Songhai Chen in the Department of Pharmacology, who has years of experiences in PDX models of breast cancer.