title: B-type proto-oncogene-mutated tumors of colon cancer: promising therapeutic approaches.
abstract: OBJECTIVE
  B-type proto-oncogene (BRAF) mutations have been observed in about 10.8% of patients with colorectal cancer (CRC). These patients do not respond to standard therapy with anti-epidermal growth factor receptor kinase (EGFR). Here we review novel BRAF inhibitors that are currently being investigated in these tumors.
  
  
  RESULTS
  Clinical experience with the BRAF inhibitor vemurafenib in CRC suggests significant differences in response compared with melanoma. Based on preclinical data, resistance to BRAF inhibitors employs alternative signaling pathways that in turn induce cell proliferation and survival. Therapeutic strategies that combine BRAF inhibitors in addition to targeted therapy with anti-EGFR monoclonal antibodies and phosphoinositide 3-kinase pathway inhibitors or standard therapy have yielded promising results in preclinical models and some reported cases.
  
  
  CONCLUSIONS
  Results from current clinical trials that are exploring novel BRAF inhibitors and others that employ combined therapy are eagerly awaited for the treatment of BRAF-mutated CRC.
  http://links.lww.com/COON/A13.
authors.affiliation: Division of Medical Oncology, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon.
authors.forename: Sally
authors.initials: S
authors.lastname: Temraz
authors.forename: Raafat
authors.initials: R
authors.lastname: Alameddine
authors.forename: Ali
authors.initials: A
authors.lastname: Shamseddine
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D058990:Molecular Targeted Therapy; D009154:Mutation / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D000090063:Proto-Oncogene Mas; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors* / Q000187:drug effects; D013449:Sulfonamides / Q000627:therapeutic use*; D000077484:Vemurafenib
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D007211:Indoles; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D013449:Sulfonamides; D000077484:Vemurafenib; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf