Targeting one-carbon metabolism requires mTOR inhibition: a new therapeutic approach in osteosarcoma

Abstract

The rate-limiting enzyme of serine biosynthesis, 3-phosphoglycerate dehydrogenase (PHGDH), contributes to rapid growth and proliferation when it is overexpressed in cancer. We recently described the metabolic adaptations that occur upon PHGDH inhibition in osteosarcoma. PHGDH inhibition causes metabolite accumulation that activates the mechanistic target of rapamycin (mTOR) signaling, sensitizing osteosarcoma to non-rapalog mTOR inhibition.

Keywords

• phgdh
• serine
• osteosarcoma
• methotrexate
• mtorc1
• perhexiline