title: The role of antiangiogenic agents in the treatment of patients with advanced colorectal cancer according to K-RAS status.
abstract: Colorectal cancer (CRC) is the fourth most commonly diagnosed cancer worldwide. Recently, it has been found that about 40 % of patients with CRC have mutations in the K-RAS gene. Several clinical trials have showed that patients with metastatic colorectal cancer (mCRC) who present tumour-promoting mutations in signalling pathways involving the epidermal growth factor receptor (EGFR), which includes activating K-RAS mutations, do not respond to anti-EGFR drugs such as panitumumab and cetuximab. Hence, K-RAS status is now considered an important negative predictive factor for response to anti-EGFR drugs. Moreover, K-RAS status seems to have also a prognostic role in CRC, but this fact is somewhat controversial. Activity of antiangiogenic agents seems not to be influenced by K-RAS gene status. Tumour angiogenesis has attracted interest in attempts to improve the management of mCRC. The vascular endothelial growth factor (VEGF) pathway is fundamental to the regulation of angiogenesis, and research has focused on developing agents that selectively target it. In this way, the anti-VEGF antibody bevacizumab in combination with chemotherapy has provided important clinical benefits in terms of response rate, progression-free survival and overall survival to patients with mCRC. Efficacy data of bevacizumab in K-RAS wild-type patients seem to be comparable with the efficacy data observed with anti-EGFR therapies in a cross-trial comparison. Although there is a lack of prospective and randomized data in this setting, the combination of chemotherapy plus antiangiogenic agents could be considered as an effective alternative for the treatment of mCRC with independence of K-RAS gene status. Here, we review the available data we have in the literature of the use of antiangiogenic strategies in the treatment of mCRC nowadays.
authors.affiliation: Medical Oncology Service, Hospital General Universitario Gregorio Marañón, C/Doctor Esquerdo, 46, 28007, Madrid, Spain, pgarcaalfonso@gmail.com.
authors.forename: Pilar
authors.initials: P
authors.lastname: García-Alfonso
authors.forename: Enrique
authors.initials: E
authors.lastname: Grande
authors.forename: Eduardo
authors.initials: E
authors.lastname: Polo
authors.forename: Ruth
authors.initials: R
authors.lastname: Afonso
authors.forename: Juan José
authors.initials: JJ
authors.lastname: Reina
authors.forename: Mónica
authors.initials: M
authors.lastname: Jorge
authors.forename: Juan Manuel
authors.initials: JM
authors.lastname: Campos
authors.forename: Virginia
authors.initials: V
authors.lastname: Martínez
authors.forename: Cristina
authors.initials: C
authors.lastname: Angeles
authors.forename: Clara
authors.initials: C
authors.lastname: Montagut
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D000077784:Axitinib; D000068258:Bevacizumab; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D000069287:Capecitabine; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D066246:ErbB Receptors / Q000378:metabolism; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D011905:Genes, ras; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage; D007191:Indazoles / Q000008:administration & dosage; D007211:Indoles / Q000008:administration & dosage; D000077146:Irinotecan; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives; D009841:Oligonucleotides; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D010597:Pharmacogenetics; D010671:Phenylurea Compounds / Q000008:administration & dosage; D011379:Prognosis; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011725:Pyridines / Q000008:administration & dosage; D011758:Pyrroles / Q000008:administration & dosage; D011799:Quinazolines / Q000008:administration & dosage; D040262:Receptors, Vascular Endothelial Growth Factor / Q000627:therapeutic use; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use; D015398:Signal Transduction; D000077157:Sorafenib; D000077210:Sunitinib; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D007093:Imidazoles; D007191:Indazoles; D007211:Indoles; D009841:Oligonucleotides; D009944:Organoplatinum Compounds; D010671:Phenylurea Compounds; D011725:Pyridines; D011758:Pyrroles; D011799:Quinazolines; D011993:Recombinant Fusion Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000077150:Oxaliplatin; D003841:Deoxycytidine; C533178:aflibercept; C559147:regorafenib; D009536:Niacinamide; D000068258:Bevacizumab; D000069287:Capecitabine; D000077146:Irinotecan; D000077157:Sorafenib; D000077784:Axitinib; C512478:EGFR protein, human; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor; C519562:imetelstat; C500926:cediranib; D005472:Fluorouracil; D000077210:Sunitinib; D002166:Camptothecin