Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2024 Feb 11;25(4):2184.
doi: 10.3390/ijms25042184.

Precision Medicine in Castration-Resistant Prostate Cancer: Advances, Challenges, and the Landscape of PARPi Therapy-A Narrative Review

George Dimitrov  1 , Radoslav Mangaldzhiev  1 , Chavdar Slavov  2 , Elenko Popov  2
Affiliations
Review

Precision Medicine in Castration-Resistant Prostate Cancer: Advances, Challenges, and the Landscape of PARPi Therapy-A Narrative Review

George Dimitrov et al. Int J Mol Sci. .

Abstract

After recent approvals, poly-adenosine diphosphate [ADP]-ribose polymerase inhibitors (PARPis) have emerged as a frontline treatment for metastatic castration-resistant prostate cancer (mCRPC). Unlike their restricted use in breast or ovarian cancers, where approval is limited to those with BRCA1/2 alterations, PARPis in mCRPC are applied across a broader spectrum of genetic aberrations. Key findings from the phase III PROPEL trial suggest that PARPis' accessibility may broaden, even without mandatory testing. An increasing body of evidence underscores the importance of distinct alterations in homologous recombination repair (HRR) genes, revealing unique sensitivities to PARPis. Nonetheless, despite the initial effectiveness of PARPis in treating BRCA-mutated tumors, resistance to therapy is frequently encountered. This review aims to discuss patient stratification based on biomarkers and genetic signatures, offering insights into the nuances of first-line PARPis' efficacy in the intricate landscape of mCRPC.

Keywords: BRCA1/2 alterations; HRR genes; PARPi; mCRPC; personalized medicine.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflicts of interest.

References

    1. Cornford P., van den Bergh R.C., Briers E., Van den Broeck T., Cumberbatch M.G., De Santis M., Fanti S., Fossati N., Gandaglia G., Gillessen S., et al. EAU-EANM-ESTRO-ESUR-SIOG guidelines on prostate cancer. Part II—2020 update: Treatment of relapsing and metastatic prostate cancer. Eur. Urol. 2021;79:263–282. doi: 10.1016/j.eururo.2020.09.046. - DOI - PubMed
    1. Leung D.K., Chiu P.K., Ng C.F., Teoh J.Y. Novel Strategies for Treating Castration-Resistant Prostate Cancer. Biomedicines. 2021;9:339. doi: 10.3390/biomedicines9040339. - DOI - PMC - PubMed
    1. Ryan C.J., Smith M.R., De Bono J.S., Molina A., Logothetis C.J., De Souza P., Fizazi K., Mainwaring P., Piulats J.M., Ng S., et al. Abiraterone in metastatic prostate cancer without previous chemotherapy. N. Engl. J. Med. 2013;368:138–148. doi: 10.1056/NEJMoa1209096. - DOI - PMC - PubMed
    1. Beer T.M., Armstrong A.J., Rathkopf D., Loriot Y., Sternberg C.N., Higano C.S., Iversen P., Evans C.P., Kim C.-S., Kimura G., et al. Enzalutamide in men with chemotherapy-naive metastatic castration-resistant prostate cancer: Extended analysis of the phase 3 PREVAIL study. Eur. Urol. 2017;71:151–154. doi: 10.1016/j.eururo.2016.07.032. - DOI - PMC - PubMed
    1. Shore N.D. Resetting the Bar of Castration Resistance—Understanding Androgen Dynamics in Therapy Resistance and Treatment Choice in Prostate Cancer. Clin. Genitourin. Cancer. 2021;19:199–207. doi: 10.1016/j.clgc.2020.08.008. - DOI - PubMed

MeSH terms

LinkOut - more resources