Planchard D, Loriot Y, Besse B
Institut Gustave-Roussy, Département de médecine, 39, rue Camille-Desmoulins, 94805 Villejuif, France.
Bull Cancer. 2009 Dec;96 Suppl:S57-68. doi: 10.1684/bdc.2009.0997.
The KRAS protein is known to play a key role in various oncogenic pathways. KRAS mutations are found in 20-30 % of patients with non-small cell lung cancer (NSCLC). The majority of mutations are found at KRAS codons 12 and 13, and they appear to be more frequent in smokers and adenocarcinoma. The mutated protein is in its active state despite absence of stimulation, which leads to the constitutive activation of downstream pathways responsible for cellular disorder. The identification of new biomarkers to predict the evolution of cancer pathogenesis (predictive factor) and the sensibility to treatments (predictive factor) is one of the major objectives in oncology research. KRAS mutations are a potential candidate biomarker and numerous studies have tried to confirm its place as a prognostic/predictive biomarker in NSCLC. The results are contradictory and most studies are retrospective. The first results of prospective studies are currently reported, in particular with the use of antibodies against EGFR. The exact place of KRAS in medical thoracic oncology remains to be determined and further studies are needed. To date, KRAS mutations are not a biomarker to be used routinely.
已知KRAS蛋白在多种致癌途径中起关键作用。在20%-30%的非小细胞肺癌(NSCLC)患者中发现KRAS突变。大多数突变发生在KRAS密码子12和13处,并且在吸烟者和腺癌患者中似乎更为常见。尽管没有刺激,突变蛋白仍处于活性状态,这导致负责细胞紊乱的下游途径的组成性激活。识别新的生物标志物以预测癌症发病机制的演变(预测因子)和对治疗的敏感性(预测因子)是肿瘤学研究的主要目标之一。KRAS突变是一种潜在的候选生物标志物,许多研究试图证实其作为NSCLC预后/预测生物标志物的地位。结果相互矛盾,大多数研究都是回顾性的。目前报道了前瞻性研究的初步结果,特别是使用抗EGFR抗体的研究。KRAS在胸部医学肿瘤学中的确切地位仍有待确定,需要进一步研究。迄今为止,KRAS突变不是一种常规使用的生物标志物。