BRAF Inhibitors in Carcinogenesis and their Clinical Implications: A Review http://www.doi.org/10.26538/tjnpr/v6i11.2
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Abstract
Mutant BRAF is a silent activator and driver of carcinogenesis. This gene is less predominant compared to frequently mutated genes implicated in cancer development. However, its occurrence in cancer has been attributed to aggressive oncogenic growth following their role in activating key oncogenic pathways, BRAF/MEK/ERK and PI3K/AKT/MTOR pathways which play crucial roles in carcinogenesis. BRAF can self-activate and drive cancer growth as a single monomer or as a dimer independent of RAS activation. A complete blockade in oncogenic BRAF will serve as a target for the development of potential therapeutic agents with no side effects. The use of BRAF inhibitors in targeting oncogenic signaling pathways has however proven inefficient due to side effects, drug resistance and relapse of the disease. The current treatment in targeting BRAF-driven oncogenesis involve the combination of BRAF inhibitors, MEK inhibitors, and immunotherapy. Resistance to BRAF inhibitors have been a serious challenge to the treatment of BRAF-linked carcinogenesis. Although, current research is targeting the use of immunotherapy as a single therapy. Other therapies with ongoing research include the use of nanotechnology for effective drug targeting and delivery at a high concentration; as well as ongoing pre-clinical trials to overcome BRAF resistance to treatment which include pre-mRNA splicing, BCL2 inhibitors, tubulin inhibitors, mitochondrial-targeted agents, polo-like kinase inhibitors and many others. This review discussed different treatment
strategies for mutant BRAF, their mode of action and the specific cancers treated as well as current trends for mutant BRAF induced cancer.
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