Sève P, Dumontet C
Inserm U. 590, pharmacogénomique et chimiorésistance, laboratoire de cytologie analytique, faculté de médecine Rockefeller, 8, avenue Rockfeller, 69373, Lyon cedex 08, France.
Rev Mal Respir. 2010 Apr;27(4):383-6. doi: 10.1016/j.rmr.2010.03.006. Epub 2010 Mar 25.
Several investigators have addressed the relationship between expression of class III beta-tubulin and outcome in patients with nonsmall cell lung cancer (NSCLC) treated with tubulin-binding agents (TBA).
High expression of class III beta-tubulin has been found to be correlated with low response rates and reduced survival in advanced NSCLC patients treated with taxane/vinorelbine--containing regimens. Two studies have shown that patients receiving paclitaxel whose tumours expressed high levels of class III beta-tubulin had a lower response rate and shorter survival, whereas this variable was not found to be predictive in patients receiving regimens without TBA. Conversely, analysis of samples from operable NSCLC patients in the JBR-10 trial showed that cisplatin/vinorelbine chemotherapy seemed to overcome the negative prognostic effect of high class III beta-tubulin expression and that the greatest benefit from chemotherapy was observed in patients with high class III beta-tubulin expression.
In advanced NSCLC, high betaIII tubulin expression may prompt selection of taxane-free regimens as the preferred initial treatment approach. The epothilones may fulfil such a role in the treatment of NSCLC.
betaIII tubulin expression is emerging as a valuable biomarker for taxane resistance in advanced disease, as well as offering prognostic information for outcomes among patients with earlier stage disease.
几位研究人员探讨了Ⅲ类β微管蛋白表达与接受微管蛋白结合剂(TBA)治疗的非小细胞肺癌(NSCLC)患者预后之间的关系。
在接受含紫杉烷/长春瑞滨方案治疗的晚期NSCLC患者中,已发现Ⅲ类β微管蛋白高表达与低缓解率和生存期缩短相关。两项研究表明,肿瘤表达高水平Ⅲ类β微管蛋白的接受紫杉醇治疗的患者缓解率较低且生存期较短,而在接受不含TBA方案治疗的患者中未发现该变量具有预测性。相反,JBR-10试验中对可手术NSCLC患者样本的分析表明,顺铂/长春瑞滨化疗似乎克服了Ⅲ类β微管蛋白高表达的负面预后影响,并且在Ⅲ类β微管蛋白高表达的患者中观察到化疗带来的最大益处。
在晚期NSCLC中,Ⅲ类β微管蛋白高表达可能促使选择不含紫杉烷的方案作为首选初始治疗方法。埃坡霉素可能在NSCLC治疗中发挥这样的作用。
Ⅲ类β微管蛋白表达正在成为晚期疾病中紫杉烷耐药的有价值生物标志物,同时也为早期疾病患者的预后提供信息。