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Int. J. Mol. Sci. 2017, 18(3), 585; doi:10.3390/ijms18030585

Strategies for Overcoming Resistance in Tumours Harboring BRAF Mutations

1
Department of Pathology, Dalhousie University, Halifax, NS B3H 4R2, Canada
2
Department of Pathology, Nova Scotia Health Authority, Halifax, NS B3H 1V8, Canada
*
Author to whom correspondence should be addressed.
Academic Editor: Terrence Piva
Received: 10 January 2017 / Revised: 7 February 2017 / Accepted: 23 February 2017 / Published: 8 March 2017
(This article belongs to the Special Issue Alterations to Signalling Pathways in Cancer Cells)
View Full-Text   |   Download PDF [442 KB, uploaded 8 March 2017]   |  

Abstract

The development of resistance to previously effective treatments has been a challenge for health care providers and a fear for patients undergoing cancer therapy. This is an unfortunately frequent occurrence for patients undergoing targeted therapy for tumours harboring the activating V600E mutation of the BRAF gene. Since the initial identification of the BRAF mutation in 2002, a series of small molecular inhibitors that target the BRAFV600E have been developed, but intrinsic and acquired resistance to these drugs has presented an ongoing challenge. More recently, improvements in therapy have been achieved by combining the use of BRAF inhibitors with other drugs, such as inhibitors of the downstream effector mitogen activated protein kinase (MAPK)/extracellular-signal regulated kinase (ERK) kinase (MEK). Despite improved success in response rates and in delaying resistance using combination therapy, ultimately, the acquisition of resistance remains a concern. Recent research articles have shed light on some of the underlying mechanisms of this resistance and have proposed numerous strategies that might be employed to overcome or avoid resistance to targeted therapies. This review will explore some of the resistance mechanisms, compare what is known in melanoma cancer to colorectal cancer, and discuss strategies under development to manage the development of resistance. View Full-Text
Keywords: BRAF; acquired resistance BRAF; acquired resistance
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Obaid, N.M.; Bedard, K.; Huang, W.-Y. Strategies for Overcoming Resistance in Tumours Harboring BRAF Mutations. Int. J. Mol. Sci. 2017, 18, 585.

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