Leveraging Novel Patient-Derived Models to Predict Therapeutic Response in Prostate Cancer

• The androgen receptor (AR) is critical to the development and progression of prostate cancer and is the primary therapeutic target. However, resistance to AR-targeted therapy is common and these patients often go on to develop lethal disease. • Understanding the mechanisms that underlie responsiveness versus resistance to AR-targeted therapies will enable the development of improved treatment strategies. • Dr. Ayesha Shafi is studying the biology of tumors from patients who were exceptional responders and exceptional non-responders to AR-targeted therapy. • Genes with a possible role in regulating responses to AR-therapy will be identified by studying animal models of prostate tumors from patients who were exceptional responders or non-responders to AR-targeted treatment. • The role of the tumor microenvironment in mediating responses vs. resistance to AR-targeted therapy will be evaluated in these models. • Dr. Shafi will also evaluate whether patient tumor samples grown in animal models can be used to predict therapeutic responses and could have a clinical role in selecting optimal treatments for patients and identifying precision medicine biomarkers. • If successful, this project will identify mechanisms of treatment response versus resistance, identify strategies for overcoming treatment resistance, and validate the use of animal models as a 'co-clinical' approach to aiding precision medicine treatment decisions.