Targeting Androgen Receptor-Bypass Mechanisms to Enhance Prostate Cancer Therapy
Abstract
My long-term career goal is to lead a team of academic scientists engaging in multidisciplinary cancer research to apply creative approaches and cutting-edge technologies, such as genome engineering, to address difficult questions and poorly understood aspects of prostate cancer progression. The training plan outlined in this proposal will equip me with the capacity to interpret large datasets such as those generated by high-throughput sequencing operations. For example, the R programming language is heavily used in the computational biology field to process and interpret genetic sequencing data. Without this training, my ability to engage in data interpretation would be severely limited. This capability is of increasing importance as the next generation of scientists addresses the exponential increase in the amount of data collected on various aspects of cancer. Given my background in advanced genome-engineering technologies, this training plan will equip me with capabilities to both model and explore the most complex and poorly understood obstructions to clinical progress in prostate cancer. This proposal is designed to address fatal gaps in our knowledge of advanced-staged prostate cancer. The groups of patients who will most benefit from this research will be those who have exhausted conventional therapeutic strategies to their prostate cancers. These patients have very limited options for alternative therapies since their stage of disease is so advanced and so poorly understood. By figuring out what to look for in patient biopsies and what to do with that knowledge once we have it, we can better manage the disease of patients who otherwise have very dire prospects. Besides decoding the complex interactions that govern how cancers adapt to treatment and advance in stage, this research proposal will help lay the groundwork for strategies that will experimentally determine the best course of treatment for every individual patient. We now know that each patient s cancer is different; by taking these differences into account when choosing treatment, we can evolve from a "one-size-fits-all" treatment paradigm to one that precisely targets the most important aspects of a patient s disease. The research outlined in this proposal may be of very near-term benefit to patients with advanced disease because we are testing the application that are already approved or in development for other cancers for their effects on a subtype of prostate cancer for which there is no effective therapy. The research proposal will also advance prostate cancer research. We will use a new approach called "CRISPR/CAS9 library screening" to studying the genetic causes of cancer, and particularly those prostate cancers that no longer rely on androgens and androgen receptor signaling and in so doing establish a platform that can continually evolve as our knowledge of cancer advances. In other words, each round of studies will improve each subsequent round of experiments so the composite data infrastructure can keep pace with the evolution of prostate cancer in the context of response and resistance to new therapeutics.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 31, 2017
- Source ID
- W81XWH1610206
Entities
People
- Michael Nyquist
Organizations
- Fred Hutchinson Cancer Center
- United States Army