EP300 degradation plus AKT inhibition shows synergy against aggressive osteosarcoma

Osteosarcoma, an aggressive bone cancer, may harbor a new therapeutic vulnerability. A St. Jude Children's Research Hospital team found that combining EP300 degradation with AKT inhibition produced a synergistic effect in patient-derived mouse xenograft models, slowing tumor growth and prolonging survival. Mechanistically, most osteosarcoma samples sensitive to EP300 degradation carried mutations that activate the AKT pathway, and sensitive tumors showed lower overall protein synthesis rates than resistant tumors. These AKT-activating mutations may serve as biomarkers identifying tumors likely to respond to the combination. The work is preclinical, based on mouse xenograft models, and the findings have not yet been tested in patients. Open questions include how the biomarker hypothesis performs in clinical samples and whether the combination can be translated into a trial-ready therapy.

Written by a model from the reports · updated 4 hours ago