Rosell Rafael, Cecere Fabiana, Santarpia Mariacarmela, Reguart Noemi, Taron Miquel
Catalan Institute of Oncology, Hospital Germans Trias i Pujol, Ctra Canyet, s/n, 08916 Badalona, Spain, and Medical Oncology Unit, University of Messina, Italy.
Curr Opin Pharmacol. 2006 Aug;6(4):323-31. doi: 10.1016/j.coph.2006.01.011. Epub 2006 Jun 12.
Lung cancer is a worldwide problem. At the time of diagnosis, 50% of patients have advanced incurable disease. Different chemotherapy combinations--with or without targeted therapies--yield similar results despite the continuous efforts of clinicians. However, molecular biological studies have already shed a great deal of light on the existence of multiple genetic aberrations that can be useful for customizing treatment. mRNA transcripts involved in DNA repair pathways, such as ERCC1 and BRCA1, confer selective resistance to cisplatin or taxanes, whereas thioredoxin confers a broad spectrum of chemoresistance. Polymorphisms in DNA repair genes and methylation of checkpoint genes in circulating serum DNA could become important predictive markers of survival in certain cisplatin-based regimens. Epidermal growth factor receptor tyrosine kinase mutations are the crux of targeted therapies, whereas epithelial-mesenchymal transitions and HER3 mRNA levels are promising ancillary markers for treatment with epidermal growth factor receptor tyrosine kinase inhibitors.
肺癌是一个全球性问题。在确诊时，50%的患者患有晚期不可治愈疾病。尽管临床医生不断努力，但不同的化疗组合（无论是否联合靶向治疗）效果相似。然而，分子生物学研究已经揭示了多种基因畸变的存在，这些畸变有助于定制治疗方案。参与DNA修复途径的mRNA转录本，如ERCC1和BRCA1，赋予对顺铂或紫杉烷的选择性耐药性，而硫氧还蛋白则赋予广泛的化疗耐药性。DNA修复基因的多态性以及循环血清DNA中检查点基因的甲基化可能成为某些基于顺铂方案中生存的重要预测标志物。表皮生长因子受体酪氨酸激酶突变是靶向治疗的关键，而上皮-间质转化和HER3 mRNA水平是表皮生长因子受体酪氨酸激酶抑制剂治疗的有前景的辅助标志物。
