Grants - V Scholar Grants - Massachusetts - 2015

Rebecca Chin, Ph.D.

Albert Wyrick V Scholar

Triple negative breast cancer (TNBC) is aggressive and has a poor prognosis. Currently, chemotherapy is the only treatment option. Therefore there is unmet need to identify novel therapeutic targets for TNBC. Acquired resistance to targeted therapy, a newer treatment type with drugs targeting specific molecules necessary for tumor growth, poses another major clinical problem. We have recently identified a major mechanism that TNBC cells utilize to promote tumor growth. This proposal aims at deciphering this mechanism in cancer growth and drug resistance, as well as discovering novel therapeutic targets for TNBC.

Akt1, Akt2 and Akt3 are a “family” of proteins with both overlapping and unique functions. Akt plays critical roles in tumor growth, and a number of drugs targeting Akt are being tested in clinical trials. Our recent findings indicate that Akt3 has an increased expression in ~30% of TNBC. Importantly, Akt3, but not Akt1/2, is critical for regulating TNBC growth. Moreover, Akt3 is implicated in drug resistance to Akt inhibitors. We propose that Akt3 regulates tumor growth and resistance by activating specific downstream targets and upregulating receptors on cell surface. To identify novel Akt3 targets, we will use a discovery-based proteomics approach. For drug resistance study, we will analyze Akt3 signaling in tumor samples, and test if certain receptor inhibitors effectively eliminate resistant cells. In the short term, our results will provide rational combination treatment strategy to combat drug resistant breast tumors. In the long term, we anticipate developing effective therapeutics targeting Akt3 or its substrates to treat TNBC.