PARP Inhibitors and Haematological Malignancies—Friend or Foe?

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 <i>BRCA</i> gene mutations. Given that PARPi act by exploiting defective DNA repair mechanisms within tumour cell...

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Autores principales:	Kathryn A. Skelding, Lisa F. Lincz
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	PARP inhibitors haematological malignancy leukaemia lymphoma DNA repair Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/618911a1190e402aa4b388aa486c5418
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spelling	oai:doaj.org-article:618911a1190e402aa4b388aa486c54182021-11-11T15:28:23ZPARP Inhibitors and Haematological Malignancies—Friend or Foe?10.3390/cancers132153282072-6694https://doaj.org/article/618911a1190e402aa4b388aa486c54182021-10-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/21/5328https://doaj.org/toc/2072-6694Since their introduction several years ago, poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) have become the standard of care for breast and gynaecological cancers with <i>BRCA</i> 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 <i>BRCA</i> 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.Kathryn A. SkeldingLisa F. LinczMDPI AGarticlePARP inhibitorshaematological malignancyleukaemialymphomaDNA repairNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5328, p 5328 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	PARP inhibitors haematological malignancy leukaemia lymphoma DNA repair Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	PARP inhibitors haematological malignancy leukaemia lymphoma DNA repair Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Kathryn A. Skelding Lisa F. Lincz PARP Inhibitors and Haematological Malignancies—Friend or Foe?
description	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 <i>BRCA</i> 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 <i>BRCA</i> 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.
format	article
author	Kathryn A. Skelding Lisa F. Lincz
author_facet	Kathryn A. Skelding Lisa F. Lincz
author_sort	Kathryn A. Skelding
title	PARP Inhibitors and Haematological Malignancies—Friend or Foe?
title_short	PARP Inhibitors and Haematological Malignancies—Friend or Foe?
title_full	PARP Inhibitors and Haematological Malignancies—Friend or Foe?
title_fullStr	PARP Inhibitors and Haematological Malignancies—Friend or Foe?
title_full_unstemmed	PARP Inhibitors and Haematological Malignancies—Friend or Foe?
title_sort	parp inhibitors and haematological malignancies—friend or foe?
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/618911a1190e402aa4b388aa486c5418
work_keys_str_mv	AT kathrynaskelding parpinhibitorsandhaematologicalmalignanciesfriendorfoe AT lisaflincz parpinhibitorsandhaematologicalmalignanciesfriendorfoe
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PARP Inhibitors and Haematological Malignancies—Friend or Foe?

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