New Roles of Poly(ADP-Ribose) Polymerase Inhibitors in the Treatment of Breast Cancer.
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ICR Authors
Authors
Harvey-Jones, E
Vinas Villaro, G
Tutt, A
Vinas Villaro, G
Tutt, A
Document Type
Journal Article
Date
2021-11-01
Date Accepted
2021-11-01
Abstract
Since the proof of concept of synthetic lethality between poly(ADP-ribose) polymerase inhibition and loss of BRCA1/2 homologous recombination (HR) function in preclinical models and early phase clinical trials, poly(ADP-ribose) polymerase inhibitors (PARPi) are increasing part of standard-of-care treatment for advanced breast cancers with BRCA gene mutations. The field has also recently seen benefits for PARPi in early breast cancer in those with germline BRCA1 and BRCA2 pathogenic mutations, and signals that synthetic lethal affects may occur in tumors with deficiencies in HR caused by germline, somatic, or epigenetic dysregulation of a number of HR genes. Despite the evidence of the synthetic lethal effects of PARPi, they are not always effective in HR defective cancers, and as they become part of standard of care in breast cancer, the study of prevalence of distinct mechanisms of resistance to PARPi and cross-resistance with other DNA-damaging agents such as platinum in breast cancer will be important and may inform therapy choices.
Citation
Cancer journal (Sudbury, Mass.), 2021, 27 (6), pp. 441 - 456
Source Title
Publisher
LIPPINCOTT WILLIAMS & WILKINS
ISSN
1528-9117
eISSN
1540-336X
1540-336X
1540-336X