The recent emergence of targeted and immunotherapeutic agents has dramatically changed the management for patients with non-small cell lung cancer (NSCLC). Despite these advances, lung cancer is not exempt from the challenges facing oncology drug development, including the huge financial cost and the time required for drug implementation. Repositioning noncancer therapies with potential antineoplastic properties into new therapeutic niches is an alternative treatment strategy offering the possibility of saving money and time and improving outcomes. The goal of such a strategy is to deliver an effective drug with a favorable toxicity profile at a reduced cost. Preclinical models and observational data have demonstrated promising activity for many of these agents, and they are now being studied in prospective trials. We review the relevant published data regarding the therapeutic effects of metformin, statins, nonsteroidal anti-inflammatory drugs, β-blockers, and itraconazole in NSCLC, with a focus on the putative mechanisms of action and clinical data. As these drugs are increasingly being tested in clinical trials, we aim to highlight the salient challenges and future strategies to optimize this approach.
摘要
最近出现的靶向和免疫治疗制剂大大改变了非小细胞肺癌(NSCLC)患者的管理。尽管取得了这些进步,但肺癌仍面临着肿瘤药物开发的挑战,其中包括巨大的财政成本和药物实施所需时间。把具有潜在抗肿瘤性质的非癌症疗法重新定位于新疗法是一种替代的治疗策略,从而可能节约成本和时间及改善预后。这种策略的目标是以降低的成本提供一种良好毒性特征谱的有效药物。临床前模型和观察性数据表明,许多这些药剂具有期望的活性,并且正在前瞻性试验中研究它们。我们回顾了关于二甲双胍、他汀类药物、非类固醇抗炎药、β受体阻滞剂以及伊曲康唑对于 NSCLC 患者的治疗效果的相关发布数据,重点是作用的假定机制和临床数据。由于越来越多地在临床试验中测试这些药物,因此我们的目标是强调突出的挑战和未来的战略来优化这种方法。 (The Oncologist) 2015;20:934–945
实践意义:与肺癌治疗药物开发相关的惊人失败率、过高成本与冗长审批过程成为探究替代策略的根据。重新定位已获批的非癌症药物来治疗非小细胞肺癌(NSCLC)是一个独特的机会, 可通过以较低的成本提供具有可管理毒性的有效药物来改善结果。几个这样的制剂已证实抗肿瘤活性,并在 NSCLC 患者人群中进行了研究。本次回顾强调了有关这些制剂治疗作用的相关文献以及推进此种策略之挑战的报告,其中包括正在进行的 I 期、II 期和 III 期试验的讨论。
Keywords: Drug repositioning; Itraconazole; Metformin; Non-small cell lung cancer; Nonsteroidal anti-inflammatory drug; Statins; β-Blocker.
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