Department of Medical Oncology, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
Drug Resist Updat. 2010 Feb-Apr;13(1-2):2-15. doi: 10.1016/j.drup.2009.11.001. Epub 2009 Dec 29.
Non-small cell lung cancer (NSCLC) is a common and often fatal malignancy, diagnosed at an advanced stage in more than half of the cases. Chemo-resistance remains a major problem in the treatment of NSCLC patients with conventional chemotherapeutic agents. Therefore main research efforts are focused on the development of novel targeted agents. In this review we provide an overview on the use of TNF-related apoptosis-inducing ligand (TRAIL) receptor targeting agents in NSCLC models and in early clinical studies. Different TRAIL receptor targeting agents are available which have been tested in NSCLC models and some were tested in the clinic. The efficacy of these drugs as single agents in NSCLC models is discussed as well as different mechanisms of resistance that are found in NSCLC cell lines. In order to maximize sensitivity to TRAIL receptor targeting drugs, combined use with other drugs is of interest. The current status of tested combinations of TRAIL receptor targeting agents with other therapeutics, such as classical cytotoxics, Bcl-2 family targeting agents, proteasome inhibitors, EGFR inhibitors, histone deacetylase inhibitors and COX-2 inhibitors as well as their mechanisms in preclinical studies are discussed. Clinical studies on TRAIL targeted therapies in which NSCLC patients were included are discussed and future perspectives are considered.
非小细胞肺癌（NSCLC）是一种常见且通常致命的恶性肿瘤，超过一半的病例在晚期才被诊断出来。化疗耐药性仍然是传统化疗药物治疗 NSCLC 患者的主要问题。因此，主要的研究重点集中在开发新的靶向药物上。在这篇综述中，我们概述了 TNF 相关凋亡诱导配体（TRAIL）受体靶向药物在 NSCLC 模型和早期临床研究中的应用。有不同的 TRAIL 受体靶向药物可供选择，这些药物已在 NSCLC 模型中进行了测试，有些药物已在临床中进行了测试。讨论了这些药物作为单一药物在 NSCLC 模型中的疗效，以及在 NSCLC 细胞系中发现的不同耐药机制。为了最大限度地提高对 TRAIL 受体靶向药物的敏感性，联合使用其他药物很有意义。讨论了目前正在测试的 TRAIL 受体靶向药物与其他治疗药物（如经典细胞毒素、Bcl-2 家族靶向药物、蛋白酶体抑制剂、EGFR 抑制剂、组蛋白去乙酰化酶抑制剂和 COX-2 抑制剂）的联合用药的现状，以及这些药物在临床前研究中的作用机制。讨论了包含 NSCLC 患者的 TRAIL 靶向治疗的临床研究，并考虑了未来的展望。
