BRAF vs RAS oncogenes: are mutations of the same pathway equal? differential signalling and therapeutic implications

// Eftychia Oikonomou 1 , Evangelos Koustas 1 , Maria Goulielmaki 1 , Alexander Pintzas 1 1 Laboratory of Signal Mediated Gene Expression, Institute of Biology, Medicinal Chemistry and Biotechnology, National Hellenic Research Foundation, Athens, 11635, Greece Correspondence to: Alexander Pintzas, e-mail: apint@eie.gr Keywords: BRAF vs KRAS, Cancer, differential signalling, targeted therapeutics, rational drug combinations to overcome resistance Received: August 04, 2014      Accepted: September 30, 2014      Published: October 21, 2014 ABSTRACT As the increased knowledge of tumour heterogeneity and genetic alterations progresses, it exemplifies the need for further personalized medicine in modern cancer management. Here, the similarities but also the differential effects of RAS and BRAF oncogenic signalling are examined and further implications in personalized cancer diagnosis and therapy are discussed. Redundant mechanisms mediated by the two oncogenes as well as differential regulation of signalling pathways and gene expression by RAS as compared to BRAF are addressed. The implications of RAS vs BRAF differential functions, in relevant tumour types including colorectal cancer, melanoma, lung cancer are discussed. Current therapeutic findings and future viewpoints concerning the exploitation of RAS-BRAF-pathway alterations for the development of novel therapeutics and efficient rational combinations, as well as companion tests for relevant markers of response will be evaluated. The concept that drug-resistant cells may also display drug dependency, such that altered dosing may prevent the emergence of lethal drug resistance posed a major therapy hindrance.