Bryant J L, Meredith S L, Williams K J, White A
Faculty of Life Sciences, Manchester Academic Health Sciences Centre, University of Manchester, AV Hill Building, Manchester M13 9PT, UK; Faculty of Medical and Human Sciences, Manchester Academic Health Sciences Centre, University of Manchester, AV Hill Building, Manchester M13 9PT, UK.
Faculty of Medical and Human Sciences, Manchester Academic Health Sciences Centre, University of Manchester, AV Hill Building, Manchester M13 9PT, UK.
Lung Cancer. 2014 Nov;86(2):126-32. doi: 10.1016/j.lungcan.2014.08.003. Epub 2014 Aug 27.
Small cell lung cancer (SCLC) is an extremely aggressive disease for which minimal therapeutic improvements have been made over the last few decades. Patients still rely on non-targeted, chemotherapeutic drugs complemented by irradiation. Although initial response is very good, the majority of SCLC patients invariably relapse with therapy-resistant tumours. Despite the link between pathologically low oxygen levels and therapy resistant tumours, hypoxia has gained little attention in the development of novel therapies for SCLC. In contrast, the advantages of targeting hypoxic cells in many other cancer types have been studied extensively. This review describes the reasons for targeting hypoxia in SCLC and outlines strategies undertaken to enhance hypoxic tumour cell death, including the use of bioreductive prodrugs, the targeting of HIF-1α and the induction of cell death through acidosis. Therapy directed towards hypoxic tumour regions has the potential to greatly enhance the response of SCLC tumours to current treatment regimens and represents an area of research in need of greater attention. Such research could lead to the much sought after development of targeted drugs against SCLC tumours.
小细胞肺癌（SCLC）是一种极具侵袭性的疾病，在过去几十年里其治疗进展甚微。患者仍依赖非靶向性化疗药物并辅以放疗。尽管初始反应非常好，但大多数小细胞肺癌患者最终都会复发，出现对治疗耐药的肿瘤。尽管病理上低氧水平与治疗耐药肿瘤之间存在关联，但缺氧在小细胞肺癌新疗法的开发中很少受到关注。相比之下，在许多其他癌症类型中靶向缺氧细胞的优势已得到广泛研究。本综述描述了在小细胞肺癌中靶向缺氧的原因，并概述了为增强缺氧肿瘤细胞死亡所采取的策略，包括使用生物还原前药、靶向缺氧诱导因子-1α（HIF-1α）以及通过酸中毒诱导细胞死亡。针对缺氧肿瘤区域的治疗有可能极大地增强小细胞肺癌肿瘤对当前治疗方案的反应，是一个需要更多关注的研究领域。此类研究可能会带来备受期待的针对小细胞肺癌肿瘤的靶向药物的开发。
