Publications Search

Search for publications by author
Search for publications by abstract keyword(s)

PARP Inhibitors in Melanoma-An Expanding Therapeutic Option?


Immunotherapy has transformed the treatment landscape of melanoma; however, despite improvements in patient outcomes, monotherapy can often lead to resistance and tumour escape. Therefore, there is a need for new therapies, combination strategies and biomarker-guided decision making to increase the subset of patients most likely to benefit from treatment. Poly (ADP-ribose) polymerase (PARP) inhibitors act by synthetic lethality to target tumour cells with homologous recombination deficiencies such as BRCA mutations. However, the application of PARP inhibitors could be extended to a broad range of BRCA-negative cancers with high rates of DNA damage repair pathway mutations, such as melanoma. Additionally, PARP inhibition has the potential to augment the therapeutic effect of immunotherapy through multi-faceted immune-priming capabilities. In this review, we detail the immunological role of PARP and rationale for combining PARP and immune checkpoint inhibitors, with a particular focus on a subset of melanoma with homologous recombination defects that may benefit most from this targeted approach. We summarise the biology supporting this combined regimen and discuss preclinical results as well as ongoing clinical trials in melanoma which may impact future treatment.

Type Journal
ISBN 2072-6694 (Print) 2072-6694 (Linking)
Authors Chan, W. Y.; Brown, L. J.; Reid, L.; Joshua, A. M.
Responsible Garvan Author Prof Anthony Joshua
Publisher Name Cancers (Basel)
Published Date 2021-09-30
Published Volume 13
Published Issue 18
Published Pages 4520
Status Published in-print
DOI 10.3390/cancers13184520
URL link to publisher's version