Better use of PARP inhibitors

BRCA1 promoter methylation predicts PARPi response in ovarian cancer: insights from the KOMET study

https://tinyurl.com/556t49sr

For ovarian cancer patients who carry the BRCA mutation, the use of PARP inhibition (PARPi) has significantly improved survival. It has been noted that some women without the BRCA mutation benefit from PARPi. This has led to a push for PARPi treatment for all. However, the cost and side effects of PARPi precludes this.

As an attempt to determine which patients benefit from PARPi, additional genomic testing known as homologous recombination deficiency (HRD) analysis shows genomic instability. Use of this has shown that up to half of the women with ovarian cancer will benefit from PARPi.

HRD analysis is expensive and may be inconclusive, meaning that it’s use is restricted. In addition, some women who might benefit from PARPi do not have the typical chromosomal mutation which causes HRD but rather have an epigenetic change called promoter methylation which stimulates the BRCA gene.

Epigenetic change is potentially reversible damage to the genetic code. In this prospective study the epigenetic methylation status testing of 88 women with ovarian cancer showed an extra 19% (17 women) who would benefit from PARPi. The authors suggest that it is possible to further identify those women who should have PARPi and avoid inappropriate use.