Targeting PHGDH Upregulation Reduces Glutathione Levels and Resensitizes Resistant NRAS-Mutant Melanoma to MAPK Kinase Inhibition

Melanomas frequently harbor activating NRAS mutations leading to activation of MAPK kinase (MEK) and extracellular signal-regulated kinase 1/2 signaling; however, the clinical efficacy of inhibitors to this pathway is limited by resistance. Tumors rewire metabolic pathways in response to stress signals such as targeted inhibitors and drug resistance, but most therapy-resistant preclinical models are generated in conditions that lack...