Targeting oncogenic BRAF and aberrant MAPK activation in the treatment of cutaneous melanoma

Matteo S Carlino; Georgina V Long; Richard F Kefford; Helen Rizos

doi:10.1016/j.critrevonc.2015.08.021

Targeting oncogenic BRAF and aberrant MAPK activation in the treatment of cutaneous melanoma

Crit Rev Oncol Hematol. 2015 Dec;96(3):385-98. doi: 10.1016/j.critrevonc.2015.08.021. Epub 2015 Aug 28.

Authors

Matteo S Carlino¹, Georgina V Long², Richard F Kefford³, Helen Rizos⁴

Affiliations

¹ Departments of Medical Oncology, Crown Princess Mary Cancer Centre, Westmead Hospital, Sydney, New South Wales, Australia; Centre for Cancer Research, Westmead Millennium Institute, Westmead, New South Wales, Australia; Melanoma Institute Australia, Sydney, New South Wales, Australia; The Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia. Electronic address: matteo.carlino@sydney.edu.au.
² Melanoma Institute Australia, Sydney, New South Wales, Australia; The Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia; The Mater Hospital, North Sydney, New South Wales, Australia.
³ Departments of Medical Oncology, Crown Princess Mary Cancer Centre, Westmead Hospital, Sydney, New South Wales, Australia; Centre for Cancer Research, Westmead Millennium Institute, Westmead, New South Wales, Australia; Melanoma Institute Australia, Sydney, New South Wales, Australia; Faculty of Medicine and Health Science, Macquarie University, New South Wales, Australia.
⁴ Centre for Cancer Research, Westmead Millennium Institute, Westmead, New South Wales, Australia; Melanoma Institute Australia, Sydney, New South Wales, Australia; Faculty of Medicine and Health Science, Macquarie University, New South Wales, Australia.

PMID: 26358420
DOI: 10.1016/j.critrevonc.2015.08.021

Abstract

BRAF and MEK inhibitors, alone or in combination, are highly active in the 40% of patients with BRAF mutant metastatic melanoma. Despite this activity resistance often develops in patients treated with these agents. This review summarises the biology of the mitogen activated protein kinase (MAPK) pathway, with particular reference to the effects of BRAF and MEK inhibitors in BRAF mutant melanoma. The clinical and molecular predictors of response and mechanisms of resistance are discussed in detail along with the biological rationale and evidence for future treatment strategies in both MAPK inhibitor naïve and resistant BRAF mutant melanoma.

Keywords: BRAF inhibitors; BRAF mutations; MEK inhibitors; Melanoma; Resistance; Targeted therapy.

Publication types

Review

MeSH terms

Humans
MAP Kinase Signaling System / drug effects*
Melanoma / drug therapy*
Melanoma, Cutaneous Malignant
Protein Kinase Inhibitors / therapeutic use*
Proto-Oncogene Proteins B-raf / antagonists & inhibitors*
Skin Neoplasms

Substances

Protein Kinase Inhibitors
Proto-Oncogene Proteins B-raf