GSTP1-Positive Subset of Prostate Cancer Overrepresented in African-American Men: Systemic Treatment Implications
Abstract
This Dr. Barbara Terry-Koroma Health Disparity Research Award application is in service of the need to reduce lethal prostate cancer, especially among African-American men. We have collected new data suggesting that a subset of prostate cancers appears to produce high levels of an enzyme called GSTP1 that helps defend cancer cells against the chemotherapy drugs most commonly used to treat life-threatening disease. Furthermore, we have found that GSTP1-producing, treatment-resistant prostate cancers are over-represented (by at least three-fold) among African-American men versus European-American men. A very similar phenomenon is well known to occur in breast cancer, where high-level expression of GSTP1 is characteristic of “triple-negative” breast cancer over-represented among young African-American women. The proposal will attempt to determine whether GSTP1-producing prostate cancers comprise the biologic basis for disparate mortality between African-American men and European-American men. The first study aim will involve a full state-of-the-art molecular characterization of GSTP1-producing prostate cancers, confirming the proclivity for this disease subset to affect African-American men and taking the first steps toward thinking about how treatment might be improved. A second aim will examine exactly how GSTP1 confers resistance to chemotherapy treatment in prostate cancer cell lines, further refining what types of treatments may best be used in the future. A final aim will assess outcomes for men with GSTP1-producing versus non-GSTP1-producing prostate cancers. The research proposed is basic in nature; the impact of the work to be undertaken on African-American men confronting life-threatening prostate cancer will likely be new strategies for treatment of a subset of the cancers that would likely have responded poorly to conventional treatment approaches. The timing of this impact depends on what is discovered in pursuit of the study aims. For instance, if the analyses reveal that a different existing anti-cancer drug might perform better for GSTP1-producing prostate cancers, new clinical trials testing its benefits could be pursued without delay. Of note in this regard, GSTP1-producing “triple-negative” breast cancers are treated differently than non-GSTP1-producing breast cancers. If, on the other hand, the data collected suggest that a new drug against a new target needs to be discovered, developed, and tested to build a treatment for GSTP1-producing prostate cancers, the full clinical impact of this project may take longer to realize. Disparities in prostate cancer incidence and mortality between African-American men and European-American men are multifaceted and complex, likely involving both inequities in access to high-quality healthcare and biologic differences in disease mechanisms. The real excitement of this project is that it focuses on a highly plausible biologic explanation for worse prostate cancer outcomes for African-American men versus European-American men. GSTP1-producing prostate cancers appear to share many attributes with GSTP1-producing breast cancers in that both may be aggressive disease variants that are chemotherapy-resistant and disproportionately arise among African-Americans. A full basic research characterization of the GSTP1-producing prostate cancers should form the basis for new, more-effective treatment approaches.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110295
Entities
People
- William C. Nelson
Organizations
- Johns Hopkins University
- United States Army