Implication of Unfolded Protein Response and Autophagy in the Treatment of BRAF Inhibitor Resistant Melanoma

E-ISSN： 1875-5992|16|3|291-298

ISSN： 1871-5206

Source： Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Anti-Cancer Agents), Vol.16, Iss.3, 2016-02, pp. : 291-298

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Abstract

The continuous activation of the mitogen-activated protein kinase signaling cascade,typified by the BRAFV600E mutation, is one of the key alterations in melanoma. Accordingly, twoBRAF inhibitors (BRAFi), vemurafenib and dabrafenib are utilized to treat melanoma and resultedin an excellent clinical outcome. However, the clinical success is not long-lasting, and the BRAFiresistance and disease progression inevitably occurs in nearly all patients. Endoplasmic reticulumstress-induced unfolded protein response and autophagy have emerged as potential pro-survival mechanisms adopted by melanoma cellsin response to BRAFi. In this review, we discuss the role of unfolded protein response and autophagy that are implicated in thedevelopment of BRAFi-resistant melanoma and the corresponding strategy aiming at overcoming the intractable clinical problem.