Theme 1: Discovery of biologic and molecular drivers of prostate cancer
Davide Ruggero, PhD identified the mTOR-eIF4E axis as a major regulator of protein translation in prostate cancer and has investigated the consequences of perturbing this axis in cancer therapeutics. In collaboration with Kevan Shokat, PhD, Ruggero developed a small molecule inhibitor of the mTOR pathway, which is being tested in early stage clinical trials by eFFECTOR Therapeutics.
Bin Liu, PhD identified CD46 as a novel target in metastatic castration-resistant prostate cancer (mCRPC) that may serve as a critical link between resistance to androgen signaling inhibition (ASI) and enhanced response to immune checkpoint inhibitors. An anti-CD46 antibody-drug conjugate (ADC) was developed with potent in vitro and in vivo activity in CRPC models. Rahul Aggarwal, MD will conduct a first-in-human trial of this ADC in mCRPC patients, sponsored by Fortis Therapeutics.
Theme 2: Biomarker and prognostic model development to predict outcomes in men with prostate cancer
Matthew Cooperberg, MD, MPH, Felix Feng, MD, and Peter Carroll, MD demonstrated the utility of five distinct prognostic and predictive genomic panels in early stage prostate cancer, several of which are now included as options in NCCN guidelines, or are being used in NCTN biomarker-stratified trials in post-prostatectomy patients.
John Kurhanewicz, PhD and Daniel Vigneron, PhD developed hyperpolarized 13C-pyruvate imaging technology in prostate cancer. In collaboration with GE Health, UCSF developed the first clinical hyper-polarizer in the world; subsequently, Sarah Nelson, PhD, Kurhanewicz, Vigneron, Small, and Carroll undertook the first application of this technology in humans in a phase I trial in prostate cancer patients followed by an ongoing multi-center phase II trial.
Theme 3: Developing therapeutic interventions to improve outcomes for men with prostate cancer
June Chan, ScD; Stacey Kenfield, ScD; Erin Van Blarigan, ScD; and Carroll demonstrated the impact of diet and lifestyle on prostate cancer outcomes in observational studies;12 developed and validated a novel comprehensive lifestyle score that includes these factors, demonstrating associations with outcome; and subsequently leveraged these findings to develop six prospective interventional trials evaluating the impact of diet and exercise in prostate cancer patients.
Charles Ryan, MD and Small evaluated abiraterone in phase I, II, and III clinical trials. The phase III study of abiraterone in men with metastatic castration resistant prostate cancer (mCRPC) without prior chemotherapy led to the FDA approval of abiraterone in this setting.