BRAF inhibitor therapy for melanoma, thyroid and colorectal cancers: development of resistance and future prospects.
BRAF is a major oncoprotein and oncogenic mutations in BRAF are found in a significant number of cancers, including melanoma, thyroid cancer, colorectal cancer and others. Consequently, BRAF inhibitors have been developed as treatment options for cancers with BRAF mutations which have shown some success in improving patient outcomes in clinical trials. Development of resistance to BRAF kinase inhibitors is common, however, overcoming this resistance is an area of significant concern for clinicians, patients and researchers alike. In this review, we identify the mechanisms of BRAF kinase inhibitor resistance and discuss the implications for strategies to overcome this resistance in the context of new approaches such as multi-kinase targeted therapies and emerging RNA interference based technologies.
Md Atiqur
MA
Rahman
Ali
A
Salajegheh
Robert Anthony
RA
Smith
Head of Pathology, Griffith Medical School, Gold Coast Campus, Gold Coast QLD 4222, Australia. a.lam@griffith.edu.au.
Alfred King-yin
AK
Lam
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D015195:Drug Design; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005544:Forecasting; D015316:Genetic Therapy / Q000379:methods / Q000639:trends; D006801:Humans; D008545:Melanoma / Q000201:enzymology / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D058990:Molecular Targeted Therapy / Q000639:trends; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D012878:Skin Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D013964:Thyroid Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology / Q000628:therapy*
D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf