Can synthetic lethality approach be used with DNA repair genes for primary and secondary MDS?

Ribeiro, Howard Lopes; Oliveira, Roberta Taiane Germano de; Borges, Daniela de Paula; Costa, Marcos Benedito Caldas; Farias, Izabelle Rocha; Santos, Antônio Wesley Araújo Dos; Magalhães, Sílvia Maria Meira; Pinheiro, Ronald Feitosa

doi:10.1007/s12032-019-1324-7

Cited by 1 publication

(1 citation statement)

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“…Myeloproliferative neoplasms (MPNs) represent a heterogeneous group of clonal diseases with a common propensity to progress to acute leukaemia. Primary MPN patient samples exhibit abnormal DNA damage responses, particularly impaired HRR [ 92 ], and therapy-related MDS (t-MDS) have a significant downregulation of the BRCA1–BRCA2–RAD51 axis compared to normal controls [ 143 ]. Taken together, this indicates that synthetic lethality may be a promising strategy for treating MPN patients.…”

Section: Parp Inhibitors As a Potential Treatment For Haematological Malignanciesmentioning

confidence: 99%

PARP Inhibitors and Haematological Malignancies—Friend or Foe?

Skelding

Lincz

2021

Cancers

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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.

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Section: Parp Inhibitors As a Potential Treatment For Haematological Malignanciesmentioning

confidence: 99%