The overarching goal of the Prostate Cancer Program is to reduce the morbidity and mortality associated with Prostate Cancer by leveraging a deep understanding of the disease at a biologic, clinical, and population level.
The Prostate Cancer Program is a multidisciplinary group of investigators focused on understanding the core biology that drives the clinical behavior of prostate cancer across the full spectrum of the disease. The Program promotes interdisciplinary research that will allow a better understanding of the biology of prostate cancer from the biologic and environmental factors associated with carcinogenesis, through the early detection and disease progression to prognostication, and the biologic basis of disease progression.
- Theme 1: Discovery of biologic and molecular drivers of prostate cancer
- Theme 2: Biomarker and prognostic model development
- Theme 3: Developing Therapeutic Interventions
Theme 1: Discovery of biologic and molecular drivers of prostate cancer
Feng, Small, Quigley, Gilbert, Bose, and Aggarwal used whole genome bisulfite sequencing to comprehensively characterize the methylation landscape of metastatic prostate cancer and discovered a novel hypermethylated subtype of metastatic disease. Quigley, Aggarwal, Small, and Feng also performed the first large-scale profiling of autoantibodies in advanced prostate cancer, utilizing a new antibody profiling approach to reveal novel cancer-specific antigens and epitopes. Huang and Cooperberg published results of single-cell sequencing analyses of prostate cancer samples, confirming presence of novel cellular subsets in these cases, and shedding light on one proposed explanation for gender disparities in terms of COVID-19 susceptibility. Feng and colleagues also interrogated the transcriptomes of thousands of prostate cancers to identify a novel interaction between the total immune content of prostate tumors and a genomic classifier of metastatic progression, to identify the most lethal subsets of patients with high-grade disease. Huang performed a large genomic study assessing for differences between prostate cancers from African American patients versus European American patients.
Theme 2: Biomarker and prognostic model development
Cooperberg and Blelloch continued work on development of plasma miRNA as prognostic biomarkers for men with localized disease. Cooperberg and Paris published findings from a DOD biomarker validation grant, finding that both DNA- and RNA-based molecular signatures in prostate tissue can together be independently prognostic. Cooperberg and Carroll developed and validated a granular prognostic model for men on active surveillance which will allow for much improved tailoring of surveillance intensity. Zhang, Small, and Feng published the first study describing outcomes associated with CDK12 mutations in prostate cancer. Hope continued to lead groundbreaking work on PSMA PET imaging for prostate cancer, including studies which led to FDA approval in 2020. Sriram, Bok, Vigneron, and Kurhanewicz utilized hyperpolarized 13C magnetic resonance spectroscopy to demonstrate elevated tumor lactate and efflux in prostate tissue slice cultures. Liu, Evans, and Flavell developed a new form of PET imaging that can detect surface expression of CD46, to utilize as a potential companion imaging tool for patients to be treated with an anti-CD46 therapy developed at UCSF.
Theme 3: Developing Therapeutic Interventions
The Program continued to build on a strong clinical research focus, developing novel interventions to improve outcomes in prostate cancer patients across the prostate cancer clinical continuum, and enhancing effective implementation strategies, including addressing cancer disparities.
For example, in active surveillance (AS) patients, Cooperberg led a series of studies focused on variation and disparity in use of active surveillance, as well as the development and submission of a multi-institutional P01 program grant aimed at assessing and improving the implementation, precision, and cost-effectiveness of active surveillance at the national level in the US. Cooperberg and Carroll undertook robust PROS analysis in AS patients.
In men with localized Prostate cancer not necessarily undergoing AS, Kenfield, Van Blarigan, Cooperberg, Carroll and Chan built on earlier observational studies and prospectively evaluated the impact of a Behavioral Change Intervention with Prostate Cancer. Cooperberg evaluated the impact of Statin use in a large outcomes data base. Feng reported Phase 3 data on the effect of chemotherapy with docetaxel with androgen suppression and radiotherapy for localized high-risk prostate cancer. Hope, Evans and Flavell have described novel work utilizing Boron Neutron Capture Therapy with Boron-containing PSMA Ligands. Aggarwal, Flavell, Small, Hope, Kurhanewicz, Noworolski, Cooperberg, Carroll, Nguyen and Seo developed and undertook a first in human Phase I Study of CTT1057, an 18F-labeled imaging agent with phosphoramidate core targeting prostatespecific membrane antigen in prostate cancer.
In men with non-metastatic recurrence, Small reported on Phase 3 data of androgen deprivation therapy with or without Apalutamide in men with non-metastatic CRPC. In men with metastatic disease, Aggarwal tested a panBET inhibitor in a Phase Ib/IIa trial, Aggarwal, Feng and Small participated in the development of targeting of MEK-ERK signaling as a therapeutic target in mCRPC.
Roster of Prostate Cancer Program
For details on membership criteria, please see our membership page.