Minimally Invasive Assessments of Prostate Cancer Molecular Heterogeneity to Direct Precision Therapy
Abstract
Scientific objectives and rationale for the proposed project: This proposal focuses on developing an accurate and minimally invasive approach for evaluating the molecular composition of metastatic castration resistant prostate cancer (mCRPC). Three key questions will be addressed in order to assist in guiding treatment decisions based on specific tumor-associated molecular features that vary between patients, and potentially between tumors within a patient: (i) Does a molecular assessment of a single metastatic site, sampled by biopsy, accurately reflect the status of other metastasis? (ii) Does a molecular assessment of a primary untreated "archival" tumor accurately identify actionable features found in advanced tumors? (iii) Do the molecular alterations found in circulating tumor cells (CTCs) accurately reflect the homogeneity and/or the diversity of molecular alterations found in the spectrum of multiple metastases in men with CRPC? The successful completion of this project will provide a means to understand treatment response and resistance based on molecular criteria and impact the deployment of precision or individualized medicine. Applicability of the research: The research studies that comprise this proposal are designed to develop a minimally invasive approach for assessing the molecular alterations that occur in a metastatic tumor. It is primarily focused on men with advanced prostate cancer. The ultimate utility involves developing a test that can assist in guiding individualized therapy based on the make-up of the tumor. A key objective of the proposal is to confirm that biomarkers acquired from a single tumor, or from circulating tumor cells, can confidently be used to make determinations for therapy. There are few risks to patients as these studies will be performed at the time of autopsy, with the exception of blood sample collections. At the conclusion of the project period, the research finding should be directly applicable to clinical care, either confirming that single biopsies and circulating tumors cells can be interpreted as a surrogate for invasive biopsies with confidence or conversely that they do not represent the diversity of molecular changes that occur in the multiple metastasis that men often have when prostate cancer spreads. What are the likely contributions of this study to advancing the field of prostate cancer research? This proposal addresses the overarching challenge of developing effective treatments and addressing mechanisms of resistance for men with metastatic prostate cancer. A key component of developing therapeutics centers on identifying treatment targets and confirming their importance across men with advanced disease. Further, understanding resistance and response is predicated on defining tumor subtypes and the extent of heterogeneity. Ideally, non-invasive or minimally invasive approaches for assessing tumor genomes (a focus area) could substantially improve our understanding of mechanisms that contribute to tumor progression and individualize treatment plans.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 29, 2016
- Source ID
- W81XWH1510430
Entities
People
- Peter S Nelson
Organizations
- Fred Hutchinson Cancer Center
- United States Army