IGF-1R inhibition: right direction, wrong pathway?
Mené sur 156 patientes atteintes d'un cancer du sein à récepteur hormonal positif de stade avancé après la ménopause, cet essai de phase II évalue l'efficacité, du point de vue de la survie sans progression, et la toxicité du gatumumab, un anticorps monoclonal anti IGF-1R, en complément d'un traitement à l'exémestane ou au fulvestrant
Inhibition of oestrogen receptor is a mainstay of treatment for oestrogen-receptor-positive breast cancer. Unfortunately, intrinsic and acquired resistance undermine the long-term effectiveness of endocrine treatments to control advanced disease and lead to relapses in early stage disease. Increased understanding of the molecular biology of breast cancer and endocrine resistance has led to a drive to develop targeted therapies and integrate them into existing treatment strategies. Oestrogen receptor signalling is linked to many other cell signalling pathways, including those related to growth hormones and insulin-like growth factor—eg, crosstalk occurs between IGF-1R and oestrogen receptor. Increased IGF signalling through the downstream Ras—MAPK and PIK3—AKT pathways can induce cellular changes necessary for motility and invasion, and increase cell survival, proliferation, and angiogenesis. Thus, combined blockade of these pathways in breast cancer is a rational strategy for clinical development...
The Lancet Oncology , commentaire en libre accès, 2012