PARP Inhibitors and Haematological Malignancies-Friend or Foe?

Abstract

Simple SummaryPARP inhibitors are a class of orally active drugs that kill a range of cancer types by inducing synthetic lethality. The usefulness of PARP inhibitors for the treatment of haematological malignancies has begun to be explored in a variety of both pre-clinical models and human clinical trials. Despite being largely considered safe and well tolerated, secondary haematological malignancies have arisen in patients following treatment with PARP inhibitors, raising concerns about their use. In this review, we discuss the potential benefits and risks for using PARP inhibitors as treatments for haematological malignancies.Since their introduction several years ago, poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) have become the standard of care for breast and gynaecological cancers with BRCA gene mutations. Given that PARPi act by exploiting defective DNA repair mechanisms within tumour cells, they should be ideally suited to combatting haematological malignancies where these pathways are notoriously defective, even though BRCA mutations are rare. To date, despite promising results in vitro, few clinical trials in humans for haematological malignancies have been performed, and additional investigation is required. Paradoxically, secondary haematological malignancies have arisen in patients after treatment with PARPi, raising concerns about their potential use as therapies for any blood or bone marrow-related disorders. Here, we provide a comprehensive review of the biological, pre-clinical, and clinical evidence for and against treating individual haematological malignancies with approved and experimental PARPi. We conclude that the promise of effective treatment still exists, but remains limited by the lack of investigation into useful biomarkers unique to these malignancies.