title: [KRAS mutation test].
abstract: KRAS mutation is detected in around 40% of colorectal cancer (CRC). Recent clinical trials revealed the ineffectiveness of anti-EGFR antibodies in CRC patients with mutated KRAS. Consequently, KRAS test is now thought to be essential to the determination of indication for anti-EGFR antibody therapy in CRC. However, there are still the following problems to be solved. (1) Prospective studies are needed to validate these clinical trial results. We recently performed KRAS genotype-driven phase II clinical trial evaluating FOLFIR/FOLFILI plus cetuximab as second-line therapy in refractory advanced CRC. KRAS codon 12 and 13 mutations were detected in 45 out of 112 patients (40.2%) for whom cetuximab was not indicated. The relation of clinical response with KRAS mutation status is now under investigation. (2) The clinical significance of the KRAS mutations except for those of codons 12 and 13 remains unclear. Clinical evaluation is necessary for KRAS codon 15, 18, 61, 117 and 146 mutations. (3) The detection methods, which are divided into sequencing and non-sequencing ones, are not standardized. Non-sequencing methods are rapid and sensitive, but costly. Furthermore, to validate their ambiguous data, sequencing methods are needed. At the present time dideoxy sequencing method seems to be preferentially chosen when considering that it is widespread and general-purposive. (4) Heterogeneous distribution of KRAS mutation in CRC tissues. (5) Effects of other genes abnormalities such as BRAF and PIK3CA mutations, PTEN down-regulation and EGFR gene amplification on the efficacy of anti-EGFR antibodies in CRC patients with or without KRAS mutation.
authors.affiliation: Department of Oncology and Laboratory Medicine, Yamaguchi University Graduate School of Medicine, Ube 755-8505, Japan. hinoda@yamaguchi-u.ac.jp
authors.forename: Yuji
authors.initials: Y
authors.lastname: Hinoda
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D017322:Clinical Trials, Phase II as Topic; D003062:Codon / Q000235:genetics; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D066246:ErbB Receptors / Q000235:genetics / Q000276:immunology*; D005820:Genetic Testing; D006801:Humans; D009154:Mutation; D010597:Pharmacogenetics; D011446:Prospective Studies; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins / Q000235:genetics*
chemical_list: D000911:Antibodies, Monoclonal; D003062:Codon; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C512478:EGFR protein, human; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins