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Current role of poly(ADP-ribose) polymerase inhibitors

which poly(ADP-ribose) polymerase inhibitor and when?

Vanacker, Hélène*; Romeo, Clémence*; Ray-Coquard, Isabelle

doi: 10.1097/CCO.0000000000000557
GYNECOLOGIC CANCER: Edited by Jean A. Klastersky
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Purpose of review In the past few years, the advent of PARP inhibitors has been a revolution in the management of ovarian cancer. Patients harboring somatic or germ line BRCA1/2 mutations exhibit different clinical and treatment response behavior. The BRCA gene is involved in repairing DNA repair via homologous recombination, and mutation of this gene leads to homologous recombination deficiency (HRD).

Recent findings HRD constitutes a therapeutic opportunity for these patients, thanks to the development of poly(ADP-ribose) polymerase inhibitors (PARPi) in the late 2000s. Indeed, using PARPi in patients with HRD simultaneously compromises two mechanisms of DNA repair, resulting in synthetic lethality.

Summary This breakthrough in clinical practice has raised remaining questions: which population will most benefit from PARPi? Are all ovarian cancers susceptible to synthetic lethal strategy? At which stage of ovarian cancer should PARPi be used? Is earlier always better? Are PARPi all equivalent? Which strategies are reasonable to overcome PARPi resistance? Which combination strategies should be efficient?

Centre Léon Berard & University Claude Bernard Lyon I, Lyon, France

Correspondence to Isabelle Ray-Coquard, Centre Léon Berard & University Claude Bernard Lyon I, Lyon, France. E-mail: isabelle.ray-coquard@lyon.unicancer.fr

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