title: New findings on primary and acquired resistance to anti-EGFR therapy in metastatic colorectal cancer: do all roads lead to RAS?
abstract: Anti-epidermal growth factor receptor therapy with the monoclonal antibodies cetuximab and panitumumab is the main targeted treatment to combine with standard chemotherapy for metastatic colorectal cancer. Many clinical studies have shown the benefit of the addition of these agents for patients without mutations in the EGFR pathway. Many biomarkers, including KRAS and NRAS mutations, BRAF mutations, PIK3CA mutations, PTEN loss, AREG and EREG expression, and HER-2 amplification have already been identified to select responders to anti-EGFR agents. Among these alterations KRAS and NRAS mutations are currently recognized as the best predictive factors for primary resistance. Liquid biopsy, which helps to isolate circulating tumor DNA, is an innovative method to study both primary and acquired resistance to anti-EGFR monoclonal antibodies. However, high-sensitivity techniques should be used to enable the identification of a wide set of gene mutations related to resistance.
authors: Department of Surgical, Oncological and Oral Sciences, University of Palermo, Palermo, Italy.
authors: Giuseppe
authors: G
authors: Bronte
authors: Medical Oncology Unit,National Cancer Institute "Giovanni Paolo II", Bari, Italy.
authors: Nicola
authors: N
authors: Silvestris
authors: Department of Surgical, Oncological and Oral Sciences, University of Palermo, Palermo, Italy.
authors: Marta
authors: M
authors: Castiglia
authors: Department of Surgical, Oncological and Oral Sciences, University of Palermo, Palermo, Italy.
authors: Antonio
authors: A
authors: Galvano
authors: Department of Surgical, Oncological and Oral Sciences, University of Palermo, Palermo, Italy.
authors: Francesco
authors: F
authors: Passiglia
authors: Department of Surgical, Oncological and Oral Sciences, University of Palermo, Palermo, Italy.
authors: Giovanni
authors: G
authors: Sortino
authors: Department of Surgical, Oncological and Oral Sciences, University of Palermo, Palermo, Italy.
authors: Giuseppe
authors: G
authors: Cicero
authors: Department of Oncology, University Hospital of Antwerp, Edegem, Belgium.
authors: Christian
authors: C
authors: Rolfo
authors: Department of Oncology, University Hospital of Antwerp, Edegem, Belgium.
authors: Marc
authors: M
authors: Peeters
authors: Department of Surgical, Oncological and Oral Sciences, University of Palermo, Palermo, Italy.
authors: Viviana
authors: V
authors: Bazan
authors: Department of Surgical, Oncological and Oral Sciences, University of Palermo, Palermo, Italy.
authors: Daniele
authors: D
authors: Fanale
authors: Sbarro Institute for Cancer Research and Molecular Medicine, Temple University, Philadelphia, PA, USA.|Department of Medicine, Surgery & Neuroscience, University of Siena, Siena, Italy.
authors: Antonio
authors: A
authors: Giordano
authors: Department of Surgical, Oncological and Oral Sciences, University of Palermo, Palermo, Italy.
authors: Antonio
authors: A
authors: Russo
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000276:immunology / Q000378:metabolism / Q000627:therapeutic use; D000068818:Cetuximab / Q000276:immunology / Q000378:metabolism / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D020558:GTP Phosphohydrolases / Q000235:genetics; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics; D009154:Mutation; D009362:Neoplasm Metastasis; D000077544:Panitumumab; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; C117307:KRAS protein, human; D008565:Membrane Proteins; D000077544:Panitumumab; C512478:EGFR protein, human; D066246:ErbB Receptors; D020558:GTP Phosphohydrolases; C579846:NRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras); D000068818:Cetuximab
keywords: RAS; cetuximab; colorectal cancer; epidermal growth factor receptor; panitumumab