Defining Overexpression of MYBL2 as a Driver of Lethal Prostate Cancer
Abstract
Prostate cancer (PCa) is the second most frequently diagnosed cancer type among men in America. Currently, the cumulative 5-year survival rate for patients with prostate cancer is over 98%. Unfortunately, the average survival for men with metastatic or recurrent prostate cancer drops considerably. Because prostate cancer is primarily driven by androgen function, therapies that inhibit androgen receptor activity are a primary focus. Second-generation therapies inhibiting the androgen receptor have provided significant life-extending therapies for recurrent or metastatic castration resistant prostate cancer (mCRPC) patients. A particular resistant, aggressive subset of these mCRPC tumors will progress to where the cancer is independent of AR activity (CRPC-AI). Overall, CRPC-AI primarily adapt to a form of prostate cancer no longer reliant on AR expression and signaling, and no current therapies are available to provide long-term response or a cure. With recent results from clinical trial data, the use of second-generation androgen receptor inhibitors will now be used earlier to treat a patient’s prostate cancer. Therefore, it is critical that we better define mechanisms that drive progression to CRPC-AI. Ultimately, this knowledge would allow for development of biomarkers to identify patients likely to progress to CRPC-AI and the discovery and validation of novel therapeutic avenues to prevent progression to CRPC-AI. With these objectives, we predict that our application would address the following FY19 PCRP Overarching Challenges: “Develop treatments that improve outcomes for men with lethal prostate cancer,” and “Define the biology of lethal prostate cancer to reduce death.” With the success of this application, we would provide an immediate clinical impact by the validation of a gene signature that would predict a patient’s immediate resistance to current second-generation androgen receptor inhibitors. We predict that by the completion of this application we will have defined the underlying biology of lethal prostate cancer driven by MYBL2 activity and nominated candidate targeted therapies to initiate clinical trials to treat patients with increased MYBL2 expression/activity.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010056
Entities
People
- Leigh Ellis
Organizations
- Cedars-Sinai Medical Center
- United States Army