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Comment
. 2018 May;10(5):e8573.
doi: 10.15252/emmm.201708573.

A novel combination treatment against melanoma with NRAS mutation and therapy resistance

Yanlin Yu  1
Affiliations
Comment

A novel combination treatment against melanoma with NRAS mutation and therapy resistance

Yanlin Yu. EMBO Mol Med. 2018 May.

Abstract

Targeted cancer therapies have shown some progress in treating BRAF‐mutant melanoma, but not against NRAS‐mutant and treatment‐resistant melanoma. In this issue of EMBO Molecular Medicine, Echevarría‐Vargas et al (2018) report that cotargeting BET and MEK pathways efficiently kills immune therapy‐resistant and NRAS‐mutant melanoma tumor cells.

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Figures

Figure 1
Figure 1. Model of the BET and MEK inhibitor combination therapy to treat melanoma with NRAS mutation and immune therapy resistance
(A) NRAS mutation constitutively activates RAF/MEK/ERK, PI3K/AKT, and Ral GEF/Ral A‐B signaling pathways and leads to BRD4 and TCF19 upregulation. The combination therapy of BET and MEK inhibitors reduces BRD4 and TCF19 expressions, which causes apoptosis of tumor cells. (B) Treatment with BRAF/MEK inhibitors or immune therapy targeting immune checkpoints (anti‐PD1 and anti‐CTLA4) shows excellent promises in melanoma only for a few cases, while melanomas with elevated TCF19 protein resist the treatment. A combined therapy of BET and MEK inhibitors causes cell cycle arrest and apoptosis through inhibition of TCF19.
See this image and copyright information in PMC

Comment on

  • Co-targeting BET and MEK as salvage therapy for MAPK and checkpoint inhibitor-resistant melanoma.
    Echevarría-Vargas IM, Reyes-Uribe PI, Guterres AN, Yin X, Kossenkov AV, Liu Q, Zhang G, Krepler C, Cheng C, Wei Z, Somasundaram R, Karakousis G, Xu W, Morrissette JJ, Lu Y, Mills GB, Sullivan RJ, Benchun M, Frederick DT, Boland G, Flaherty KT, Weeraratna AT, Herlyn M, Amaravadi R, Schuchter LM, Burd CE, Aplin AE, Xu X, Villanueva J. Echevarría-Vargas IM, et al. EMBO Mol Med. 2018 May;10(5):e8446. doi: 10.15252/emmm.201708446. EMBO Mol Med. 2018. PMID: 29650805 Free PMC article.

References

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