BRAF as a therapeutic target: a patent review (2006 - 2012)

• Published in: Expert opinion on therapeutic patents Vol. 23; no. 2; p. 155
• Main Authors: Zambon, Alfonso, Niculescu-Duvaz, Dan, Niculescu-Duvaz, Ion, Marais, Richard, Springer, Caroline J
• Format: Journal Article
• Language: English
• Published: England 01.02.2013
• Subjects: Animals; Antineoplastic Agents - chemistry; Antineoplastic Agents - therapeutic use; Drug Design; Drug Resistance, Neoplasm - genetics; Humans; Molecular Structure; Molecular Targeted Therapy; Mutation; Neoplasms - diagnosis; Neoplasms - drug therapy; Neoplasms - enzymology; Neoplasms - genetics; Patents as Topic; Patient Selection; Precision Medicine; Predictive Value of Tests; Protein Kinase Inhibitors - chemistry; Protein Kinase Inhibitors - therapeutic use; Proto-Oncogene Proteins B-raf - antagonists & inhibitors; Proto-Oncogene Proteins B-raf - genetics; Proto-Oncogene Proteins B-raf - metabolism; Signal Transduction - drug effects
• ISSN: 1744-7674
• DOI: 10.1517/13543776.2013.741593

After its identification as an oncogene in 2002, mutant BRAF has become the target of a number of drug discovery programmes, primarily aimed at the treatment of late stage or unresectable melanoma. Some of the drugs thus developed, such as vemurafenib and dabrafenib, show impressive responses in melanoma patients harbouring a BRAF mutation. This review summarises the patent literature on BRAF from 2006 to 2012, focusing on the specific areas of inhibitors of mutant BRAF, drug combinations including BRAF inhibitors, diagnostic methods for use with mutant BRAF inhibitors & diagnosis and treatment of mutant BRAF cancers resistant to BRAF inhibitors. Whilst these first-generation BRAF inhibitors initially mediate excellent responses in late stage or unresectable melanoma patients bearing the V600 mutation, resistance usually occurs and patients eventually relapse. The patent literature for new BRAF inhibitors and therapies reflects the desire to develop second-generation drugs able to overcome this resistance and combination treatments that increase the efficiency of current mutant BRAF inhibitors.