Targeting protein disulfide isomerase to overcome resistance to BRAF inhibitors in melanoma

Changes in the cellular redox state is one mechanism by which the cell integrates information and coordinates complex signaling pathways involved in tumor progression. Melanoma is the most aggressive form of skin cancer. Half of the patients tumors have the BRAF V600E mutation and develop resistance to the treatment with the BRAF inhibitor vemurafenib (iBRAF). Targeting redox-regulated signaling pathways activated in melanoma may represent a new approach in the treatment of this disease. We first found that Nox4 and protein disulfide isomerase (PDI) are highly expressed in melanoma (n=54) when compared to non-malignant nevus (n=27) (p