title: Biomarkers of skin toxicity induced by anti-epidermal growth factor receptor antibody treatment in colorectal cancer.
abstract: Skin toxicity is a common symptom of anti-epidermal growth factor receptor (EGFR) antibody treatment and is also a predictive marker of its efficacy in colorectal cancer patients. However, severe skin disorders induced by such antibodies negatively impact on the quality of life of patients and decreases drug compliance during treatment. If we can predict the high-risk group susceptible to severe skin toxicity before treatment, we can undertake the early management of any arising skin disorders and formulate a more accurate prognosis for anti-EGFR antibody treatment. Previous studies have identified molecular markers of skin toxicity induced by anti-EGFR antibody, such as EGFR polymorphisms, the expression of inflammatory chemokines and serum levels of EGFR ligands. A clinical trial was undertaken involving the escalation of cetuximab doses, guided by the grade of skin toxicity observed, such as no or low-grade, in metastatic colorectal cancer (the EVEREST study). The dose escalation of cetuximab was confirmed by a safety profile and had the tendency to achieve a higher response rate in KRAS wild-type patients. A large, prospective randomized trial is now ongoing (EVEREST 2) and the results of this trial may contribute to personalized medicine in KRAS wild-type colorectal cancer patients.
authors.affiliation: Akiko Kubo, Hironobu Hashimoto, Division of Pharmacy, National Cancer Center Hospital, Tokyo 104-0045, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Kubo
authors.affiliation: Akiko Kubo, Hironobu Hashimoto, Division of Pharmacy, National Cancer Center Hospital, Tokyo 104-0045, Japan.
authors.forename: Hironobu
authors.initials: H
authors.lastname: Hashimoto
authors.affiliation: Akiko Kubo, Hironobu Hashimoto, Division of Pharmacy, National Cancer Center Hospital, Tokyo 104-0045, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Takahashi
authors.affiliation: Akiko Kubo, Hironobu Hashimoto, Division of Pharmacy, National Cancer Center Hospital, Tokyo 104-0045, Japan.
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Yamada
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D000068818:Cetuximab / Q000008:administration & dosage / Q000009:adverse effects*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D003875:Drug Eruptions / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D006801:Humans; D058990:Molecular Targeted Therapy / Q000009:adverse effects; D009154:Mutation; D010641:Phenotype; D011237:Predictive Value of Tests; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D012307:Risk Factors; D012867:Skin / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; C117307:KRAS protein, human; C512478:EGFR protein, human; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras); D000068818:Cetuximab
keywords: Colorectal cancer; Epidermal growth factor receptor; Epidermal growth factor receptor polymorphism; Ligand; Skin toxicity
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