Limitations of homologous recombination status testing and poly (ADP-ribose) polymerase inhibitor treatment in the current management of ovarian cancer
Recognition of the importance of defective DNA repair (DDR) as the cause for most ovarian cancer has radically changed the prospects for survival. Initially demonstrated as the basis for hereditary breast and ovarian cancer through the BRCA genetic mutation, DDR is the target for personalised therapy with enzyme inhibition using PARPi.
It is now realised that DDR is much more common and the basic defect is described as homologous recombination deficiency (HRD), which is not confined to the BRCA mutation. It is possible to test directly for HRD and this has increased the number of women who have been assigned personalised therapy.
However, there are problems; not all HRD women respond to PARPi, many develop resistance to the drug and it is unclear whether overall survival is improved.
Partly this is due to the inaccuracies of HRD testing, the current test produces a score for homologous proficiency (HRP). It seems that HRP is complex with partial genetic penetration. There is more to learn about HRD.
No comments:
Post a Comment