Advanced prostate cancer patients are initially treated with androgen deprivation therapy, which blocks a key pathway for prostate cancer survival. Eventually, most patients will fail prostate cancer therapy and progress to castrate resistant prostate cancer, the lethal form of the disease. Approximately 26,000 men will succumb to castrate resistant prostate cancer this year. In the Grabowska laboratory, we are working to improve prostate cancer patient outcomes through understanding the “who”, “what”, and “how” of prostate cancer progression. We are exploring how prostate cancer progresses to castrate resistance. We are also exploring who will fail androgen deprivation therapy and what new drugs and therapies we can develop or repurpose to help these patients. Our studies utilize human derived prostate cancer cell lines, pre-clinical models, and human prostate cancer specimens.
Our funded studies focus on transcription factors, which are proteins that bind to DNA and determine what genes are turned on or off. We are interested in how a specific transcription factor family, the nuclear factor I (NFI) family, interacts with androgen receptor. Androgen receptor is the target of androgen deprivation therapy and the major therapeutic target in prostate cancer. Therefore, understanding how androgen receptor activity is regulated is critical for determining how patients fail androgen deprivation therapy. Our previous studies have demonstrated that the NFI family can control androgen receptor activity, and our current work focuses on determining how this control changes during therapeutic failure in prostate cancer.