title: Current and advancing treatments for metastatic colorectal cancer.
abstract: BACKGROUND
  Colorectal cancer (CRC) is one of the leading causes of cancer deaths worldwide. Despite the introduction of several new drugs targeting the vascular endothelial growth factor or epidermal growth factor receptor (EGFR) signaling pathways, survival and disease control in metastatic CRC remains poor.
  
  
  METHODS
  Chemotherapy based on fluoropyrimidines and irinotecan or oxaliplatin has been the cornerstone of CRC standard of care for several decades. Optimal regimens are selected according to toxicity profiles and patient characteristics. The addition of targeted drugs inhibiting angiogenesis, notably bevacizumab, aflibercept and ramucirumab, has improved chemotherapy outcomes in metastatic CRC. Anti-EGFR agents, cetuximab and panitumumab, in combination with chemotherapy have also improved survival in patients with wild-type RAS tumors. In the refractory setting, there are emerging drugs such as regorafenib or TAS-102 that also have demonstrated impact on outcomes.
  
  
  CONCLUSIONS
  Drugs targeting signaling pathways involved in tumorigenesis improve patient outcomes over chemotherapy alone. Determining the most suitable combination and sequence should be carefully selected, with studies yet to provide a definitive solution to this unknown. Molecular mechanisms of colorectal cancer are at the forefront of research. Knowledge in this domain will help overcome resistance to therapies and introduce new drugs in the personalized CRC therapeutic scenario.
authors.affiliation: a Department of Medical Oncology , Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona , 08035 Barcelona , Spain.
authors.forename: Enrique
authors.initials: E
authors.lastname: Sanz-Garcia
authors.affiliation: b Department of Medical Oncology , Vall d'Hebron Institute of Oncology , 08035 Barcelona , Spain.|c Department of Medical Oncology , Instituto Català de Oncologia , 08907 Barcelona , Spain.
authors.forename: Julieta
authors.initials: J
authors.lastname: Grasselli
authors.affiliation: a Department of Medical Oncology , Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona , 08035 Barcelona , Spain.|b Department of Medical Oncology , Vall d'Hebron Institute of Oncology , 08035 Barcelona , Spain.
authors.forename: Guillem
authors.initials: G
authors.lastname: Argiles
authors.affiliation: a Department of Medical Oncology , Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona , 08035 Barcelona , Spain.|b Department of Medical Oncology , Vall d'Hebron Institute of Oncology , 08035 Barcelona , Spain.
authors.forename: M Elena
authors.initials: ME
authors.lastname: Elez
authors.affiliation: a Department of Medical Oncology , Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona , 08035 Barcelona , Spain.|b Department of Medical Oncology , Vall d'Hebron Institute of Oncology , 08035 Barcelona , Spain.
authors.forename: Josep
authors.initials: J
authors.lastname: Tabernero
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000627:therapeutic use; D002166:Camptothecin / Q000031:analogs & derivatives / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D004338:Drug Combinations; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000276:immunology; D006801:Humans; D000077146:Irinotecan; D009362:Neoplasm Metastasis; D009944:Organoplatinum Compounds / Q000627:therapeutic use; D000077150:Oxaliplatin; D000077544:Panitumumab; D011759:Pyrrolidines; D040262:Receptors, Vascular Endothelial Growth Factor / Q000627:therapeutic use; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use; D035703:Therapies, Investigational / Q000379:methods / Q000639:trends; D013941:Thymine; D014271:Trifluridine / Q000627:therapeutic use; D014498:Uracil / Q000031:analogs & derivatives / Q000627:therapeutic use; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000276:immunology; D000096662:Ramucirumab
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000068258:Bevacizumab; D002166:Camptothecin; D004338:Drug Combinations; D066246:ErbB Receptors; D000077146:Irinotecan; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000077544:Panitumumab; D011759:Pyrrolidines; D040262:Receptors, Vascular Endothelial Growth Factor; D011993:Recombinant Fusion Proteins; D013941:Thymine; D014271:Trifluridine; D014498:Uracil; D042461:Vascular Endothelial Growth Factor A; D000096662:Ramucirumab; C000613803:trifluridine tipiracil drug combination; C533178:aflibercept; C512478:EGFR protein, human
keywords: 5-fluoruracil; EGFR; MAPK; VEGFR; aflibercept; bevacizumab; cetuximab; colorectal cancer; irinotecan; oxaliplatin; panitumumab; ramucirumab; regorafenib