Sangha Randeep, Lara Primo N, Mack Philip C, Gandara David R
University of California, Davis Cancer Center, 4501 X Street, Suite 3016, Sacramento, CA 95817, USA.
Curr Opin Oncol. 2009 Mar;21(2):116-23. doi: 10.1097/CCO.0b013e3283210489.
Integrating targeted therapies against the epidermal growth factor receptor (EGFR) and angiogenesis pathways into standard treatment paradigms for advanced nonsmall cell lung cancer (NSCLC) have been successful, but not yet curative. Two treatment strategies, in development, seem particularly appealing for further study: insulin-like growth factor receptor (IGF-1R) and histone deacetylase (HDAC) inhibition. Several lines of evidence suggest that these novel approaches may play a relevant role in the future treatment of NSCLC.
Preliminary results of a phase II trial combining an anti-IGF-1R monoclonal antibody with platinum-based chemotherapy in untreated NSCLC patients have shown an encouraging response rate, particularly in those with squamous cell carcinoma, where IGFR expression is typically high. Recent data also support the clinical development of HDAC inhibitors as a strategy to counter epigenetic gene silencing and transcriptional repression of key anticancer genes. Moreover, research efforts are focusing on identifying predictive markers to appropriately select patients for maximal therapeutic benefit.
Here, we briefly review data regarding anti-EGFR and antiangiogenesis agents before discussing the potential roles for IGF-1R and HDAC inhibitors in NSCLC management, and the need for optimizing treatment by seeking a more personalized approach to care.
将针对表皮生长因子受体（EGFR）和血管生成途径的靶向治疗纳入晚期非小细胞肺癌（NSCLC）的标准治疗模式已取得成功，但尚未达到治愈效果。正在研发的两种治疗策略似乎特别值得进一步研究：胰岛素样生长因子受体（IGF-1R）抑制和组蛋白去乙酰化酶（HDAC）抑制。多项证据表明，这些新方法可能在NSCLC的未来治疗中发挥重要作用。
一项II期试验的初步结果显示，在未经治疗的NSCLC患者中，将抗IGF-1R单克隆抗体与铂类化疗联合使用，反应率令人鼓舞，特别是在鳞状细胞癌患者中，这类患者的IGFR表达通常较高。近期数据也支持将HDAC抑制剂作为一种对抗关键抗癌基因的表观遗传基因沉默和转录抑制的策略进行临床开发。此外，研究工作正集中于确定预测标志物，以便适当选择患者以获得最大治疗益处。
在此，我们在讨论IGF-1R和HDAC抑制剂在NSCLC治疗中的潜在作用以及通过寻求更个性化的治疗方法来优化治疗的必要性之前，简要回顾有关抗EGFR和抗血管生成药物的数据。
