Targeting PHGDH upregulation reduces glutathione levels and re-sensitizes resistant NRAS mutant melanoma to MEK inhibition

Melanomas frequently harbor activating NRAS mutations leading to activation of MEK-ERK1/2 signaling; however, clinical efficacy of inhibitors to this pathway are limited by resistance. Tumors re-wire metabolic pathways in response to stress signals such as targeted inhibitors and drug resistance, but most therapeutic resistant pre-clinical models are generated in conditions that lack physiological metabolism. We generated human NRAS mutant melanoma xenografts that were resistant to the MEK inhibitor (MEKi), PD0325901, in vivo.

Source: Journal of Investigative Dermatology - May 6, 2020 Category: Dermatology Authors: Mai Q. Nguyen, Jessica L.F. Teh, Timothy J. Purwin, Inna Chervoneva, Michael A. Davies, Katherine L. Nathanson, Phil F. Cheng, Mitchell P. Levesque, Reinhard Dummer, Andrew E. Aplin Tags: Original Article Source Type: research