Emerging Strategies for Therapy of Metastatic Brain Cancer

PROJECT SUMMARY Brain cancer remains a devastating disease and in particular, brain metastases (BM) from breast cancer represent the leading cause of fatality for women. The major hindrance to significant clinical benefit for BM is the poor permeability of monoclonal antibodies (i.e. trastuzumab) across the blood brain barrier (BBB), resulting in

surgical resection and radiation therapies as the first line therapeutic options. With our team of experienced and highly accomplished scientists with strong track record in basic, translational, and clinical research, we propose to advance the science of metastases to the brain by focusing on 1) understanding of fundamental biology of

HER2+ breast cancer metastases to the brain via patient tissue-based genetic dissection of risk factors 2) the advancement in real-time of visualization of cancer cells and neural stem cells (NSCs) targeting HER2+ BM and 3) the application of targeted NSC delivery of trastuzumab analogs to suppress the growth of HER2+ BM. The

novel paradigm established by this application will advance our understanding of how cancer cells invade and spread thru the brain and potentially help herald an era of genetically engineered stem cells as targeted delivery conduit for anti-HER2 therapy against HER2+ BM.