PARP-ish: Gaps in Molecular Understanding and Clinical Trials Targeting PARP Exacerbate Racial Disparities in Prostate Cancer
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Published on: December 9, 2015
Moriah L Cunningham1,2, Matthew J Schiewer1,3,2
1Department of Urology, Thomas Jefferson University, Philadelphia, Pennsylvania.
Abstract:
PARP is a nuclear enzyme with a major function in the DNA damage response. PARP inhibitors (PARPi) have been developed for treating tumors harboring homologous recombination repair defects that lead to a dependency on PARP. There are currently three PARPi approved for use in advanced prostate cancer, and several others are in clinical trials for this disease. Recent clinical trial results have reported differential efficacy based on the specific PARPi utilized as well as patient race. There is a racial disparity in prostate cancer, in which African American males are twice as likely to develop and die from the disease compared with European American males. Despite the disparity, there continues to be a lack of diversity in clinical trial cohorts for prostate cancer. In this review, PARP nuclear functions, inhibition, and clinical relevance are explored through the lens of racial differences. This review will touch on the biological variations that have been explored thus far between African American and European American males with prostate cancer to offer a rationale for investigating PARPi response in the context of race at both basic science and clinical development levels.
Insights
Poly (ADP-ribose) polymerase inhibitors (PARPi) show varied effectiveness in prostate cancer, particularly concerning race. Research is needed to understand biological differences and improve PARPi treatment for African American men.
Area of Science:
- Oncology
- Genetics
- Pharmacology
Background:
- Poly (ADP-ribose) polymerase (PARP) is crucial for DNA damage response.
- PARP inhibitors (PARPi) target tumors with homologous recombination repair defects.
- Three PARPi are approved for advanced prostate cancer, with more in trials.
Purpose of the Study:
- To review PARP functions, inhibition, and clinical relevance in prostate cancer.
- To explore the impact of racial differences on PARPi efficacy.
- To provide a rationale for investigating PARPi response in diverse populations.
Main Methods:
- Review of existing literature on PARP, PARPi, and prostate cancer.
- Analysis of clinical trial data regarding differential efficacy and patient race.
- Exploration of biological variations between African American and European American men with prostate cancer.
Main Results:
- Recent clinical trials show differential PARPi efficacy based on patient race.
- African American men face a higher incidence and mortality from prostate cancer.
- Clinical trial cohorts often lack racial diversity.
Conclusions:
- Racial disparities in prostate cancer necessitate investigation into race-based PARPi responses.
- Understanding biological variations is key to optimizing PARPi treatment across populations.
- Further research at basic science and clinical levels is required to address these disparities.
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