title: Recent Advances in Targeting the EGFR Signaling Pathway for the Treatment of Metastatic Colorectal Cancer.
abstract: Outcomes for metastatic colorectal cancer (mCRC) patients have been improved by treatment with anti-epidermal growth factor receptor (anti-EGFR) antibodies, particularly when combined with predictive biomarkers to select patients lackingRASmutations. New technologies such as liquid biopsy and next-generation sequencing have revealed that potential mechanisms of resistance to anti-EGFR therapies act through acquired mutations ofKRASand theEGFRectodomain. Mutations in cross-talking molecular effectors that participate in downstream EGFR signaling are also negative predictors for anti-EGFR therapy. In the current review, we describe recent advances in anti-EGFR therapy and discuss new treatment strategies to target downstream RAS-MAPK signaling in mCRC.
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556, Japan. miyamotoyuji@gmail.com.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Miyamoto
authors.affiliation: Cancer Center, Kumamoto University Hospital, Kumamoto 860-8556, Japan. kou_susan@yahoo.co.jp.
authors.forename: Koichi
authors.initials: K
authors.lastname: Suyama
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556, Japan. hdobaba@kumamoto-u.ac.jp.
authors.forename: Hideo
authors.initials: H
authors.lastname: Baba
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods* / Q000639:trends; D009154:Mutation; D009362:Neoplasm Metastasis; D016283:Proto-Oncogene Proteins p21(ras) / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics
chemical_list: D000911:Antibodies, Monoclonal; C117307:KRAS protein, human; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras)
keywords: chemotherapy; epidermal growth-factor receptor signaling (EGFR); metastatic colorectal cancer; secondary resistance