sapanisertib + telaglenastat

The combination of sapanisertib and telaglenastat is an investigational drug therapy being studied primarily for non-small cell lung cancer (NSCLC). This combination targets specific metabolic pathways in cancer cells, particularly in tumors with certain genetic mutations. Sapanisertib (MLN0128) is a dual mTORC1/2 inhibitor that targets the mammalian target of rapamycin (mTOR) pathway, which is involved in cell growth and metabolism. It inhibits glycolysis in cancer cells. Telaglenastat (CB-839 HCl) is a first-in-class oral glutaminase inhibitor that blocks tumor glutamine consumption. Glutaminase is a mitochondrial enzyme that converts glutamine to glutamate, which cancer cells use for biosynthesis, proliferation, and regulation of oxidative stress. The combination works synergistically because when glycolysis is inhibited by mTOR inhibition with sapanisertib, cancer cells typically switch to glutamine metabolism to fuel the Krebs cycle. By simultaneously blocking glutaminolysis with telaglenastat, this adaptive metabolic switch is prevented, potentially enhancing anti-tumor effects.