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Olaparib and rucaparib for the treatment of DNA repair-deficient metastatic castration-resistant prostate cancer
- Source :
- Expert Opin Pharmacother
- Publication Year :
- 2021
- Publisher :
- Informa UK Limited, 2021.
-
Abstract
- INTRODUCTION: Metastatic prostate cancer is a heterogeneous disease characterized by clinical and genomic heterogeneity. Many prostate cancers harbor mutations causing DNA repair deficiency, specifically homologous recombination deficiency, sensitizing to drugs that inhibit poly ADP-ribose polymerase (PARP). PARP is an enzyme that is involved in single-stranded DNA repair and is the target of newly approved treatments for metastatic prostate cancer. AREAS COVERED: Here, the authors’ review the clinical trials leading to the recent approvals of two PARP inhibitors (PARPi), olaparib and rucaparib, specifically TOPARP-A, TOPARP-B, PROfound and TRITON-2. They also compare the different FDA approvals for both of these medications and outline the safety of this class of drugs in prostate cancer. EXPERT OPINION: Because PARPi are particularly effective in men with somatic or germline alterations in BRCA1 and BRCA2, we recommend that all men be tested for DNA alterations with next-generation sequencing in tumor cells obtained from either tissue or blood. We also recommend that olaparib or rucaparib be considered relatively early in the treatment sequence in metastatic castration-resistant prostate cancer patients with BRCA1 or BRCA2 mutations. Other DNA alterations might also sensitize to PARPi though the response rates are lower, so other standard therapies should be prioritized first.
- Subjects :
- Male
Indoles
DNA Repair
DNA repair
Antineoplastic Agents
Disease
Castration resistant
Article
Piperazines
Olaparib
03 medical and health sciences
chemistry.chemical_compound
Prostate cancer
0302 clinical medicine
Prostate
medicine
Humans
Pharmacology (medical)
Rucaparib
Pharmacology
business.industry
General Medicine
medicine.disease
Prostatic Neoplasms, Castration-Resistant
medicine.anatomical_structure
chemistry
030220 oncology & carcinogenesis
PARP inhibitor
Cancer research
Phthalazines
business
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 17447666 and 14656566
- Volume :
- 22
- Database :
- OpenAIRE
- Journal :
- Expert Opinion on Pharmacotherapy
- Accession number :
- edsair.doi.dedup.....f673705fb661ebc9c62549756e27e145