The evolving landscape of predictive biomarkers of response to PARP inhibitors

J Clin Invest. 2018 May 1;128(5):1727-1730. doi: 10.1172/JCI120388. Epub 2018 Apr 16.

Abstract

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.

Publication types

  • Research Support, N.I.H., Intramural
  • Comment

MeSH terms

  • Biomarkers
  • Carcinoma, Ovarian Epithelial*
  • Female
  • Humans
  • Ovarian Neoplasms*
  • Poly(ADP-ribose) Polymerase Inhibitors
  • Positron-Emission Tomography

Substances

  • Biomarkers
  • Poly(ADP-ribose) Polymerase Inhibitors