Identifying Genomic Drivers of Prostate Cancer Progression and Drug Resistance in Tumors and Circulating DNA
Abstract
Scientific Objective: Despite significant advances in therapy, metastatic prostate cancer remains a lethal disease. A better understanding of the biological basis of prostate cancer will be needed to develop new treatment approaches and improve outcomes for patients. In order to understand the genetic basis of prostate cancer, recent large projects have reported DNA changes (genomic alterations) that occur in early and advanced disease. These projects, made possible by developments in DNA sequencing technology, revealed previously unknown genomic alterations that may eventually be used to target the disease with new drugs. However, it is unclear how these genomic alterations affect the progression of the disease, and how they affect tumor response to therapies that we commonly use to treat it. Understanding the role of these genomic changes in disease progression and drug resistance will be critical to developing new targeted treatments. Our project will integrate genomic data with clinical data (patient treatment history and responses to therapy) to determine the role of these genomic alterations in disease progression and drug resistance. This is now possible, given the availability of large genomic data sets, as well as clinical information about patients included in these data sets. We have unique access to these data sets, which are not available elsewhere, and we are well-positioned to determine how changes in DNA affect relevant patient outcomes. Applicability of the Research: The research proposed here has direct applicability to patients with prostate cancer. The prostate cancer therapies, enzalutamide and abiraterone, were developed based on a better understanding of prostate cancer biology, and we are now in a position to determine the role of DNA alterations in disease progression and outcomes for patients. These DNA alterations are already being tested for in the clinic through commercial tests, but it is not yet clear how to interpret and make use of many of these findings. At the conclusion of our project, we will have clinical and biologic insight into the role of many of these genomic alterations in driving the disease, which will lead to better use of these tests and new treatment approaches. Expected Contributions of the Study to Prostate Cancer Research: The discovery of frequent genomic alterations in prostate cancer in the TCGA and SU2C studies was a significant advance in the field, but how these alterations affect patient outcomes remains a key unanswered question. The study we propose here will address this question using unpublished SU2C genomic and clinical data, as well as a large data set from our institution. Our study will identify important genomic drivers of progression and drug resistance that will lead to further laboratory-based studies of mechanism and new clinical trial approaches. Career Goals: I am a new faculty member at Memorial Sloan Kettering Cancer Center who is focused on treating patients with prostate cancer and on research in the disease. Part of my work involves clinical trials using new therapies. The key to the success of these trials will be a better understanding of the biology of the disease, as well as the identification of patients who are most likely to benefit from a specific therapy. I plan to spend my career investigating these questions, both by studying prostate cancer genomics and other aspects of its biology and by developing clinical trials based on biological findings. Support for this project by the Department of Defense will be critical to my professional development toward this goal.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Aug 07, 2017
- Source ID
- W81XWH1710124
Entities
People
- Wassim Abida
Organizations
- Memorial Sloan Kettering Cancer Center
- United States Army