PARP inhibitors elicit distinct transcriptional programs in homologous recombination competent castration-resistant prostate cancer.
Publication/Presentation Date
2-1-2026
Abstract
Prostate cancer (PCa) is the second most lethal cancer in men in the US. African American (AA) men have twice the incidence and death rate of European American (EA) men. Advanced PCa shows increased expression and activity of the DNA damage/repair pathway enzyme, poly (ADP-ribose) polymerase 1 (PARP1). PARP1 inhibitors (PARPi) are FDA-approved for advanced PCa tumors with mutations in the homologous recombination repair (HRR) pathway. However, PARPi can provide benefit in model systems without HRR deficiencies. PARPi have distinct biochemical mechanisms, potencies, and toxicity profiles. While there is emerging evidence of differences in DNA damage/repair pathway enzyme expression between EA and AA men, PARP1 expression has not been fully explored in the context of race. This study hypothesized: (a) AA and EA PCa may respond differently to PARPi and (b) different PARPi may uniquely impact the transcriptome, irrespective of HRR status. Study results indicate a link between racial background and PARP1 expression/activity and define unique and overlapping transcriptional responses downstream of all five PARPi. These findings may lead to refined personalized recommendations for use of specific PARPi.
Volume
20
Issue
2
First Page
369
Last Page
388
ISSN
1878-0261
Published In/Presented At
Cunningham, M. L., Vasquez-Gonzalez, J., Barnada, S. M., Tchotorlishvili, S., Jones, L., Maguire, R., Lewis, G., Rizwan, K., Deng, J., Koachar, S., Patel, D., Shankle, H., Mulders, T., Ajmal, N., Solomides, C., Alnemri, E. S., Alnemri, T. F., Shafi, A. A., Gomella, L. G., Kelly, W. K., … Schiewer, M. J. (2026). PARP inhibitors elicit distinct transcriptional programs in homologous recombination competent castration-resistant prostate cancer. Molecular oncology, 20(2), 369–388. https://doi.org/10.1002/1878-0261.70098
Disciplines
Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods
PubMedID
40915979
Department(s)
Administration and Leadership
Document Type
Article