Article

The potential for BRAF V600 inhibitors in advanced cutaneous melanoma: rationale and latest evidence.

Sarah Cannon Research UK, London and University College London, London, UK.
rapeutic Advances in Medical Oncology, The 03/2012; 4(2):61-73. DOI:10.1177/1758834011432949 pp.61-73
Source: PubMed

ABSTRACT Historically, patients with advanced cutaneous melanoma have a poor prognosis and limited treatment options. The discovery of selective v-raf murine sarcoma viral oncogene homolog B1 (BRAF) V600 mutation as an oncogenic mutation in cutaneous melanoma and the importance of the mitogen-activated protein kinase (MAPK) pathway in its tumourigenesis have changed the treatment paradigm for melanoma. Selective BRAF inhibitors and now MEK inhibitors have demonstrated response rates far higher than standard chemotherapeutic options and we review the phase I-III results for these agents in this article. The understanding of mechanisms of resistance that may occur upstream, downstream, at the BRAF level or bypassing the MAPK pathway provides a platform for rational drug development and combination therapies.

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Keywords

bypassing
 
combination therapies
 
cutaneous melanoma
 
downstream
 
Historically
 
limited treatment options
 
oncogenic mutation
 
phase I-III results
 
rational drug development
 
selective v-raf murine sarcoma viral oncogene homolog B1
 
treatment paradigm
 
tumourigenesis
 

Charlotte Lemech