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, two
BRAF inhibitors (BRAFi), vemurafenib and dabrafenib are utilized to treat melanoma and resulted
in an excellent clinical outcome. However, the clinical success is not long-lasting, and the BRAFi
resistance and disease progression inevitably occurs in nearly all patients. Endoplasmic reticulum
stress-induced unfolded protein response and autophagy have emerged as potential pro-survival mechanisms adopted by melanoma cells
in response to BRAFi. In this review, we discuss the role of unfolded protein response and autophagy that are implicated in the
development of BRAFi-resistant melanoma and the corresponding strategy aiming at overcoming the intractable clinical problem.