The Effect of Androgen Metabolism by Gastrointestinal Microbiota on Resistance to Androgen Receptor Axis-Targeted Therapies in Metastatic Prostate Cancer
Abstract
We are only now beginning to understand the magnitude of the influence of the microbiome, the collection of microorganisms that live on and within our bodies, on cancer outcomes. One new mechanism that we are proposing by which the microbiome that exists in our gastrointestinal (GI) tract may influence prostate cancer outcomes is interfering with the hormone-targeted therapies used in men with metastatic prostate cancer. Whereas most hormone-ablating therapies work well initially in men with metastatic disease, the cancer inevitably comes back. We hypothesize that this may be driven in part by the under-recognized capability of the microorganisms in the GI tract to produce hormones that are absorbed into the bloodstream, rendering the therapies ineffective. We are proposing a study in samples collection from men with metastatic prostate cancer, whereby we will examine fecal and serum hormone levels in relation to disease progression. Our ultimate goal is to develop strategies to modulate the GI microbiome to overcome primary resistance to or prolong the clinical response to hormone-targeted therapies for men with metastatic prostate cancer. Therefore, our proposal addresses the FY19 Prostate Cancer Research Program Overarching Challenge of developing treatments that improve outcomes for men with lethal prostate cancer. Since our study is being conducted in patient samples, if our hypothesis is correct, there can be an immediate move to develop new therapeutic strategies.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010274
Entities
People
- Karen S Sfanos
Organizations
- Johns Hopkins University
- United States Army