The evolving landscape of predictive biomarkers of response to PARP inhibitors

• Published in: The Journal of clinical investigation Vol. 128; no. 5; pp. 1727 - 1730
• Main Authors: Thomas, Anish, Murai, Junko, Pommier, Yves
• Format: Journal Article
• Language: English
• Published: United States American Society for Clinical Investigation 01.05.2018
• Subjects: Biomarkers; Biomedical research; Breast cancer; Cancer therapies; Carcinoma, Ovarian Epithelial; Chemotherapy; Deoxyribonucleic acid; DNA; DNA biosynthesis; DNA damage; DNA methylation; DNA repair; Enzymes; Female; Humans; Medical imaging; Mutation; Niacinamide; Ovarian cancer; Ovarian Neoplasms; Patients; Poly(ADP-ribose); Poly(ADP-ribose) polymerase; Poly(ADP-ribose) Polymerase Inhibitors; Polymers; Positron-Emission Tomography; Prostate cancer; Proteins; Ribose; Rodents
• ISSN: 0021-9738; 1558-8238
• DOI: 10.1172/jci120388

Poly(ADP-ribose) polymerase inhibitors (PARPis) are DNA-damaging agents that trap PARP-DNA complexes and interfere with DNA replication. Three PARPis - olaparib, niraparib, and rucaparib - were recently approved by the FDA for the treatment of breast and ovarian cancers. These PARPis, along with 2 others (talazoparib and veliparib), are being evaluated for their potential to treat additional malignancies, including prostate cancers. While lack of PARP-1 confers high resistance to PARPis, it has not been established whether or not the levels of PARP-1 directly correlate with tumor response. In this issue of the JCI, Makvandi and coworkers describe an approach to address this question using [18F]FluorThanatrace, an [18F]-labeled PARP-1 inhibitor, for PET. The tracer was taken up by patient tumor tissue and appeared to differentiate levels of PARP-1 expression; however, future studies should be aimed at determining if this tracer can be used to stratify patient response to PARPi therapy.