Abiraterone plus olaparib in prostate cancer: a new form of synthetic lethality?
Mené dans 11 pays sur 142 patients atteints d'un cancer de la prostate résistant à la castration et de stade métastatique, cet essai de phase II évalue l'efficacité, du point de vue de la survie sans progression, et la toxicité de l'ajout de l'olaparib à l'abiratérone
The advent of poly(ADP-ribose) polymerase (PARP) inhibitors, which have been approved for the treatment of ovarian and breast cancers, represents an important advancement in the treatment of cancers harbouring DNA-repair deficiency mutations. The synthetic lethality hypothesis has been used to explain the mechanism underlying the activity of these drugs. This hypothesis postulates that pharmacological inhibition of PARP1 (involved in single-strand DNA damage repair via the base-excision repair pathway) in cancer cells that harbour biallelic inactivating mutations in homologous recombination genes, such as BRCA2, will result in accumulation of catastrophic DNA damage, resulting in tumour cell apoptosis.
The Lancet Oncology , commentaire, 2017