Genomic predictors of clinical outcomes and benefit of (chemo)hormonal therapy in metastatic hormone sensitive prostate cancer
Abstract
This proposed research project seeks to address a key FY19 PCRP Overarching Challenge of better defining the biology of lethal prostate cancer. Most men who are diagnosed with prostate cancer present with localized tumors that may be managed with surveillance, surgery, or radiation. Some men, however, present with evidence of metastasis at first diagnosis or after previous treatment. In recent years, we have made important advances in the treatment of newly diagnosed metastatic prostate cancer by combining testosterone-lowering therapy with chemotherapy (chemohormonal therapy) or newer hormonal agents. However, despite men living longer, metastatic prostate cancer remains a lethal disease. To date, our understanding of which men benefit from chemohormonal therapy is limited. Importantly, there is mounting evidence that specific changes (mutations) in prostate cancer genes may strongly determine treatment benefit and survival. This study seeks to resolve these two observations by determining whether gene mutations predict benefit, less benefit, or non-benefit of hormonal therapy and chemohormonal therapy in patients diagnosed with metastatic prostate cancer. Critically, this study aims to determine the gene mutations that are linked to poorer outcomes and to specifically ask whether patients with evidence of these mutations in tumor biopsies need upfront treatment with chemohormonal therapy. We have the unique opportunity to determine this by using tumor biopsies from the two most important clinical trials of chemohormonal therapy that changed practice worldwide: CHAARTED and STAMPEDE. By informing the use of chemohormonal therapy with great precision, this study will directly help improve the care of patients with newly diagnosed metastatic prostate cancer by identifying patients who are most likely to need treatment, as well as identifying those unlikely to benefit, and these men could therefore avoid the burden and side effects of chemotherapy. In addition, we believe gene mutations will identify a subgroup of men with more aggressive prostate cancer for which (1) information regarding prognosis will better inform their patient journey and treatment choices and (2) there is a critical need to develop and test new treatments and treatment combinations that may be tailored to their gene profile. Ultimately, we believe this study will directly inform clinical practice by guiding clinicians and patients in choosing a more optimal and precise strategy for treating metastatic prostate cancer. Given that tumor biopsies have been collected and linked with clinical information, and we have received support to initiate the training phase of the study, we also believe the time frame of 2 years for study completion is appropriate and feasible. The research project strongly supports Dr. Hamid’s overarching career goal to develop as an innovative and impactful principal investigator (PI) and clinician-scientist. Dr. Hamid continued to develop expertise in prostate cancer biology, data analysis, and interpretation that is reflected by completion of strong preliminary studies that have directly informed the design of the research plan. The proposed study builds upon the preliminary work he has led by addressing these questions in two clinical trial cohorts. By completion of the study, Dr. Hamid will have further developed important skills and expertise in cancer genetics and analysis that will directly support his independence as a PI of considerable distinction in the prostate cancer research community. The development of his career and support of his goals is strongly supported by an outstanding research environment at Dana-Farber Cancer Institute, which is evidenced by excellent mentorship and collaborations established during his early postdoctoral fellowship. Dr. Hamid is mentored by Professor Christopher Sweeney, a leader in prostate cancer research and the PI of two practice-changing clinical trials of metasta
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010055
Entities
People
- Anis A Hamid
Organizations
- Dana–Farber Cancer Institute
- United States Army