Winter 2014 – Vemurafenib: Background, Patterns of Resistance, and Strategies to Combat Resistance in Melanoma
Vemurafenib: Background, Patterns of Resistance, and Strategies to Combat Resistance in Melanoma.
Arjun Dupati* and Liza Gill
College of Human Medicine, Michigan State University, East Lansing, MI, USA
*Corresponding author: Arjun Dupati; dupatiar[at]gmail.com
Arjun Dupati and Liza Gill contributed equally to the production of this manuscript.
Key Words: Vemurafenib; Molecular Targeted Therapy; Melanoma Drug Resistance; Metastatic Melanoma; Tyrosine Kinase Inhibitor; Melanoma Treatment.
Introduction: Finding an effective treatment for metastatic melanoma has posed a series of challenges. Vemurafenib, a B-RAF tyrosine kinase inhibitor, has been one of the most successful medications to date in the treatment of metastatic melanoma. B-RAF is a serine/threonine kinase that is a part of the RAS-RAF-MEK-ERK signal transduction pathway, which plays a pivotal role in cellular proliferation, differentiation, and survival. Mutations in the B-RAF protein lead to a deregulated activation of MAPK and ERK.
The focus of this review article is resulting resistance to vemurafenib and its clinical implications on the treatment of metastatic melanoma. This paper aims to highlight mechanisms of vemurafenib resistance that have been observed so far and offer potential clinical approaches to overcome resistance.
Methods: PubMed, Google Scholar, and EMBASE were searched using the following free text terms: “vemurafenib,” “vemurafenib resistance,” “vemurafenib tyrosine-kinase inhibitor,” “vemurafenib metastatic melanoma,” “vemurafenib alternatives,” and “vemurafenib cancer.” The Cochrane database was searched for randomized controlled trials and systematic reviews using the same search terms above. Two independent reviewers analyzed the search results and corresponding articles.
Discussion: Research over the last decade, most notably in the past two years has revealed a multitude of mechanisms of resistance to vemurafenib. Resistance to therapy with vemurafenib in metastatic melanoma could be explained by the presence of cancer stem cells.
Conclusion: In order to effectively circumvent resistance, it would behoove clinicians to approach metastatic melanoma with a cocktail of inhibitors as opposed to monotherapy.
Published: January 1, 2014
Senior Editor: Kailyne Van Stavern
Junior Editor: Kaitlyn Vitale
Dupati A, Gill L. Vemurafenib: Background, Patterns of Resistance, and Strategies to Combat Resistance in Melanoma. Medical Student Research Journal. 2014;3(Winter):36-43.
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