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Cancers 2015, 7(3), 1900-1924; doi:10.3390/cancers7030868

Therapy for BRAFi-Resistant Melanomas: Is WNT5A the Answer?

Cell and Experimental Pathology, Department of Translational Medicine, Lund University, Clinical Research Centre, Skåne University Hospital, Malmö SE-20502, Sweden
These authors contributed equally to this work.
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Author to whom correspondence should be addressed.
Academic Editor: Chyi-Chia Richard Lee
Received: 23 June 2015 / Revised: 9 September 2015 / Accepted: 14 September 2015 / Published: 17 September 2015
(This article belongs to the Special Issue Current Topics in Cutaneous Melanoma)
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Abstract

In recent years, scientists have advocated the use of targeted therapies in the form of drugs that modulate genes and proteins that are directly associated with cancer progression and metastasis. Malignant melanoma is a dreadful cancer type that has been associated with the rapid dissemination of primary tumors to multiple sites, including bone, brain, liver and lungs. The discovery that approximately 40%–50% of malignant melanomas contain a mutation in BRAF at codon 600 gave scientists a new approach to tackle this disease. However, clinical studies on patients have shown that although BRAFi (BRAF inhibitors) trigger early anti-tumor responses, the majority of patients later develop resistance to the therapy. Recent studies have shown that WNT5A plays a key role in enhancing the resistance of melanoma cells to BRAFi. The focus of the current review will be on melanoma development, signaling pathways important to acquired resistance to BRAFi, and why WNT5A inhibitors are attractive candidates to be included in combinatorial therapies for melanoma. View Full-Text
Keywords: melanoma; WNT5A; BRAFi; MAPK/ERK; PI3K-AKT; MITF melanoma; WNT5A; BRAFi; MAPK/ERK; PI3K-AKT; MITF
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Prasad, C.P.; Mohapatra, P.; Andersson, T. Therapy for BRAFi-Resistant Melanomas: Is WNT5A the Answer? Cancers 2015, 7, 1900-1924.

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