Targeting chondrosarcoma and osteosarcoma cell metabolism : the IGF pathway and beyond

Abstract

Thesis explored potential new therapeutic strategies by

identifying cellular pathways that are essential for chondrosarcoma and

osteosarcoma cell survival. Although clinical trials with IGF1R inhibitors

have disappointing results in osteosarcoma, this thesis strengthens the view that the IGF pathway can be an effective target for osteosarcoma therapy if an appropriate selection of patients is treated with IGF1R/IR dual inhibitors. When optimized clinical trials targeting the IGF pathway will be performed in the future, chondrosarcoma patients should not be recruited, as there is limited preclinical rationale for the efficacy of IGF1R targeting agents in chondrosarcoma. We identified two promising pathways that can be used to target chondrosarcoma; the NAD+ synthesis pathway and glutaminolysis. Our results suggest that chondrosarcoma patients should be included in future studies with drugs that interfere in these pathways, regardless of their IDH1/2 mutation status.