Carvalho Lina, Silva António, Andrade Cláudia, Barroso Cláudia, Farinha Cláudia, Fernandes José Carlos, Landeiro Raquel
Anatomia Patológica/Oncologia, Faculdade de Medicina, Universidade de Coimbra, Portugal.
Rev Port Pneumol. 2009 Jul-Aug;15(4):683-96. doi: 10.1016/s0873-2159(15)30164-1.
In lung cancer, expressive survival has not yet been achieved in non surgical stages. Non-small cell lung cancer (NSCLC) patients are treated with platinum and other drugs. To choose these agents we can actual ly define predictive biomarkers to preview therapeutic response. A literature revision was done in order to define the role of ERCC1 e RRM1 genes in the response to chemotherapy based in platinum and gemcitabine respectively. The expression of these genes is faced as a predictive marker to the chemotherapy response in patients with adenocarcinomas and squamous cell carcinomas, providing a personalized therapy. Published data supports this behaviour and is useful to individualize therapy accordingly to individual levels of ERCC1 which are modified by genetic mutations. Polymorphisms in codons 118 C/T and C8092A, seem to influence the carcinogenesis, cytostatic resistance, survival and even the prognosis. Clinical and laboratorial trials showed that high expression of RRM1 gene in NSCLC has impact in the tumoral phenotype. Patients having done surgical resection and presenting high expression of RRM1 have better survival than those with lower expression. However, patients with advanced NSCLC and treated with chemotherapy with gemcitabine and cisplatin appear to have a poor outcome if the tumor express elevated levels of RRM1 gene.
在肺癌中,非手术阶段尚未实现表达性生存。非小细胞肺癌(NSCLC)患者接受铂类和其他药物治疗。为了选择这些药物,我们实际上可以定义预测性生物标志物来预测治疗反应。进行了一项文献综述,以分别确定ERCC1和RRM1基因在基于铂类和吉西他滨的化疗反应中的作用。这些基因的表达被视为腺癌和鳞状细胞癌患者化疗反应的预测标志物,从而提供个性化治疗。已发表的数据支持这种情况,并且根据因基因突变而改变的ERCC1个体水平来个性化治疗是有用的。密码子118 C/T和C8092A的多态性似乎会影响致癌作用、细胞生长抑制抗性、生存率甚至预后。临床和实验室试验表明,NSCLC中RRM1基因的高表达对肿瘤表型有影响。接受手术切除且RRM1表达高的患者比表达低的患者生存率更高。然而,如果肿瘤表达高水平的RRM1基因,晚期NSCLC患者接受吉西他滨和顺铂化疗似乎预后较差。