Phenotype switching in melanoma: implications for progression and therapy

• Main Authors: Frederic Zhentao Li, Amardeep Singh Dhillon, Robin eAnderson, Grant eMcArthur, Petranel Theresa Ferrao
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2015-02-01
• Series: Frontiers in Oncology
• Subjects: Drug Resistance; Melanoma; metastasis; targeted therapy; BRAF; EMT
• Online Access: http://journal.frontiersin.org/Journal/10.3389/fonc.2015.00031/full

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