Extending the scope of PARP inhibitors in ovarian cancer
Mené sur 34 patientes atteintes d'un cancer épithélial de l'ovaire ou d'un cancer du sein, cet essai de phase Ib évalue la dose maximale tolérée et la toxicité de l'olaparib (un inhibiteur de PARP) en combinaison avec l'alpélisib (un inhibiteur de PI3K)
In the past decade, trials with inhibitors of oral poly (ADP-ribose) polymerase (PARP), a key enzyme involved in the repair of DNA damage, have led to a major change in the treatment of advanced ovarian cancer. A key element of the success of this class of drug is deficiency in the homologous recombination repair (HRR) pathway, which repairs DNA double-strand breaks. This deficiency is often seen in BRCA-mutated tumours, since functioning BRCA proteins have a major role in preserving the complex DNA repair pathway. However, other mechanisms apart from BRCA mutations can also result in HRR pathway alterations and consequently lead to a clinical benefit from PARP inhibitors. 1
Study of DNA damage response and manipulation of the process is now recognised as an important area of research and could lead to better cancer treatments. 2
Precise measurement of HRR is difficult, but in ovarian cancer it is most closely related to the platinum sensitivity of the tumour. Tumours that become platinum resistant—an inevitable consequence of recurrence—rarely respond to PARP inhibitors.
The Lancet Oncology , commentaire, 2018