PDX Trial Center for Breast Cancer Therapy

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Project Summary The scientific premise of this Center is that breast cancer patient-derived xenograft (PDX) and organoid models represent the diversity of human breast tumors, and can be feasibly utilized to test new drugs and drug combinations to find therapeutic approaches that match with molecular features of various tumor types. Our PDTC is focused on identifying new treatment strategies for breast cancer, which remains the 2nd leading cause of cancer death in women. We will conduct preclinical evaluation of drugs and drug combinations in models selected from our large collection of 261 breast PDX models and >100 stable PDxO lines representing primary, metastatic, and treatment-resistant breast cancers from diverse patient populations (25% of the collection is from racial/ethnic minorities, with plans to increase that proportion in Aim 1 of both research projects). The Center comprises two highly integrated Research Projects that are designed together to combat the two most difficult problems contributing to breast cancer deaths: breast cancer recurrence, and treatment of recurrent/metastatic disease. More than 90% of breast cancer deaths are attributed to disease recurrence as incurable metastatic disease. Project 1 is focused on improving therapy for early-stage triple negative breast cancer (TNBC), to prevent recurrence and achieve durable cures by identifying optimal chemotherapy and targeted therapy combinations based on molecular features of tumors. Project 2 aims to identify more effective regimens in disease that does recur (treatment-resistant, metastatic disease) by utilizing our unique collection of PDX and PDxO from metastatic samples. These two complementary research projects will be supported by a PDX Core, a Bioinformatics Core, a Pilot Projects and Trans-Network Activities Core that fosters exploration of new ideas within the PDTC and in collaboration with the PDXNetwork (PDXNet), and an Administrative Core that provides project oversight and management, and facilitates effective communication within the PDTC and the PDXNet. The overarching goal of our PDX Development and Trials Center (PDTC) is to obtain preclinical data that will facilitate prioritization of drugs to be tested in breast cancer clinical trials at the National Cancer Institute (NCI).