Homologous Recombination Deficiency Assays in Epithelial Ovarian Cancer: Current Status and Future Direction
Sometimes progress in the care of patients with ovarian cancer seems painfully slow. Then new understanding begins to show a way forward. One such innovation was the appreciation that much cancer starts due to a failure of repair in the DNA that makes up the cell nucleus. Cellular DNA is under constant attack from within and without. If DNA is not repaired cells will usually die but sometimes the cell line continues as a cancer.
Faulty DNA repair, known as Homologous Recombination Deficiency (HRD) is seen with BRCA1/2 mutation and sometimes with other acquired mutations, being present in about 50% of all ovarian cancer. As a consequence another enzyme; Polyadenosine Ribonucleotide Polymerase (PARP) becomes more important in DNA repair. Repair by PARP is less exact and sometimes may prolong cancer, a concept known as synthetic lethality.
This understanding of the biology of ovarian cancer has led to new treatment with drugs that inhibit PARP (PARPi). Up to 40% of patients with BRCA mutation do not respond to PARPi. So, better testing for HRD is needed. Currently the HRD status of individuals is inferred from the mutation. Unfortunately this does not predict PARPi response. An HRD test hopefully will better show who will benefit from PARPi
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