On-Target Efficacy of a HIF2alpha Antagonist in Preclinical Kidney Cancer Models
Menée sur des modèles précliniques de carcinome rénal à cellules claires et sur un patient, ces deux études mettent en évidence des mécanismes d'activité antitumorale d'un composé appelé PT2399, un inhibiteur du facteur de transcription HIF-2alpha
Clear cell renal cell carcinoma (ccRCC), the most common form of kidney cancer, is usually linked to inactivation of the pVHL tumor suppressor protein and consequent accumulation of the HIF2α transcription factor. Here we show that a small molecule (PT2399) that directly inhibits HIF2α causes tumor regression in preclinical models of primary and metastatic pVHL-defective ccRCC in an on-target fashion. pVHL-defective ccRCC cell lines display unexpectedly variable sensitivity to PT2399, however, suggesting the need for predictive biomarkers.
Nature , résumé, 2015