title: [Predictive biomarkers for anti-EGFR antibodies].
abstract: The clinical significance of KRAS gene testing prior to using anti-epidermal growth factor receptor(EGFR)antibodies for colorectal cancer patients has been established in past randomized clinical trials. Thus, testing for the 7 most common mutations of KRAS codons 12 and 13 is now recommended as a clinical practice. However, pooled analysis of randomized controlled studies in Western countries in patients treated with cetuximab has suggested that patients with tumors showing the KRAS p. G13D mutation[a glycine(G)to aspartate(D)transition mutation] have longer overall survival and progression-free survival when compared to patients with other KRAS mutations. Furthermore, even among patients whose tumors are wild-type for KRAS codons 12 and 13, response rates are only 13~17% for anti-EGFR antibody monotherapy. These facts suggest that additional activating mutations in the RAS-RAF-MAPK or PI3K-AKT-mTOR pathways may also confer resistance to anti-EGFR antibody therapies. Indeed, recent retrospective studies have shown that mutations in KRAS codon 61 and 146, BRAF, NRAS, and PIK3CA may also predict resistance to anti-EGFR antibodies in colorectal cancer patients. On the other hand, the continuous use of anti-EGFR therapies for KRAS wild-type patients may lead to secondary resistance. Acquired EGFR or KRAS mutations have occasionally been detected among specimens from these patients. We review the latest personalized therapy available for colorectal cancer patients using KRAS mutational testing. We also illustrate future perspectives for patient selection using KRAS, BRAF, NRAS, PIK3CA, and other mutations.
authors.affiliation: Dept. of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Chiba 277-8577, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Bando
authors.forename: Takayuki
authors.initials: T
authors.lastname: Yoshino
mesh_terms: D000888:Antibodies, Anti-Idiotypic / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D066246:ErbB Receptors / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D015398:Signal Transduction / Q000187:drug effects*; D018631:ras Proteins / Q000235:genetics
chemical_list: D000888:Antibodies, Anti-Idiotypic; D014408:Biomarkers, Tumor; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins