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Review
. 2015 Feb 13:5:31.
doi: 10.3389/fonc.2015.00031. eCollection 2015.

Phenotype switching in melanoma: implications for progression and therapy

Frederic Zhentao Li  1 , Amardeep Singh Dhillon  2 , Robin L Anderson  3 , Grant McArthur  4 , Petranel T Ferrao  2
Affiliations
Review

Phenotype switching in melanoma: implications for progression and therapy

Frederic Zhentao Li et al. Front Oncol. .

Abstract

Epithelial-mesenchymal transition (EMT) is a key process associated with the progression of epithelial cancers to metastatic disease. In melanoma, a similar process of phenotype switching has been reported and EMT-related genes have been implicated in promotion to a metastatic state. This review examines recent research on the role of signaling pathways and transcription factors regulating EMT-like processes in melanoma and their association with response to therapy in patients, especially response to BRAF inhibition, which is initially effective but limited by development of resistance and subsequent progression. We highlight studies implicating specific roles of various receptor tyrosine kinases (RTKs) in advancing melanoma progression by conferring a proliferative advantage and through promoting invasive phenotypes and metastasis. We also review the current knowledge of the mechanisms underlying resistance to BRAF inhibition and the potential role of melanoma phenotype switching in this process. In particular, we discuss how these important new insights may significantly enhance our ability to predict patterns of melanoma progression during treatment, and may facilitate rational development of combination therapies in the future.

Keywords: BRAF inhibition; EMT; RTK signaling; melanoma; metastasis; phenotype switching; resistance.

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Figures

Figure 1
Figure 1
A schematic diagram of the signaling and molecular features of melanoma phenotype switching. The EMT-like phenotype switching confers melanoma invasive functions. The EMT-associated signaling in melanoma is also implicated in conferring resistance to BRAF inhibition therapies in BRAF-mutant metastatic melanoma.
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