Genetics to epigenetics: targeting histone deacetylases in hormone receptor-positive metastatic breast cancer
Mené en Chine sur 365 patientes atteintes d'un cancer du sein HR+ HER2- de stade avancé après la ménopause, cet essai de phase III évalue l'efficacité, du point de vue de la survie sans progression, et la toxicité d'un traitement combinant tucidinostat (un inhibiteur d'histone désacétylase) et exémestane (durée médiane de suivi : 13,9 mois)
During the past decade, the use of combination targeted therapies for hormone receptor-positive, HER2-negative metastatic breast cancer has increased substantially. Besides approval of mTOR and CDK4 and CDK6 inhibitors in combination with endocrine therapy as second-line or later treatment, positive results have been reported with an
α-specific PI3K inhibitor, alpelisib, in combination with endocrine therapy for patients with hormone receptor-positive, HER2-negative, metastatic breast cancer who have PIK3CA mutations. In addition to genetic alterations, epigenetic modification via histone deacetylases (HDACs) is another putative mechanism by which gene expression patterns can be changed, leading to cellular growth and proliferation. In preclinical models of endocrine-resistant breast cancer, HDAC inhibition can restore oestrogen receptor dependency on, and sensitivity to, anti-oestrogens, highlighting the potential therapeutic role of HDAC inhibitors in endocrine-resistant metastatic breast cancer.
The Lancet Oncology , commentaire, 2018