Lallo Alice, Schenk Maximilian W, Frese Kristopher K, Blackhall Fiona, Dive Caroline
Clinical and Experimental Pharmacology Group, Cancer Research UK Manchester Institute, University of Manchester, Manchester, UK.
Institute of Cancer Sciences, University of Manchester and Christie NHS Foundation Trust, Manchester, UK.
Transl Lung Cancer Res. 2017 Aug;6(4):397-408. doi: 10.21037/tlcr.2017.08.01.
Lung cancers are the main cause of cancer-related deaths worldwide. Efforts placed to improve the survival of lung cancer patients and untangle the complexity of this disease, have resulted in the generation of hundreds of lung cancer cell lines and several genetically engineered mouse models (GEMMs). Although these research tools have extended our knowledge of lung cancer, improvement in the clinical care of lung cancer patients have been limited overall, with measured optimism regarding initial responses to targeted therapies in stratified subgroups of patients. Patient-derived xenograft (PDX) models are beginning to assist 'personalized therapy' approaches particularly in non-small cell lung cancer (NSCLC) however biopsies of lung cancers to generate PDXs are not without challenges and risks to the patient. Liquid biopsies, on the other hand, are a rapid and non-invasive procedure allowing the collection of circulating tumor cells (CTCs) with a single 10 mL blood draw. These CTCs recapitulate the molecular heterogeneity of the corresponding tumors and, therefore, can be used as surrogates to study tumor biology and generate new patient-derived models. Here, we discuss the CTC-derived models that have been generated, most notably in small cell lung cancer (SCLC), highlighting challenges and opportunities related to these novel preclinical tools.
肺癌是全球癌症相关死亡的主要原因。为提高肺癌患者生存率并厘清该疾病的复杂性所做的努力，已产生了数百种肺癌细胞系和多种基因工程小鼠模型（GEMMs）。尽管这些研究工具扩展了我们对肺癌的认识，但肺癌患者临床护理的总体改善仍然有限，对于分层亚组患者对靶向治疗的初始反应仅持适度乐观态度。患者来源的异种移植（PDX）模型开始助力“个性化治疗”方法，尤其是在非小细胞肺癌（NSCLC）中，然而获取肺癌活检样本以建立PDX并非没有挑战，且对患者存在风险。另一方面，液体活检是一种快速且非侵入性的程序，只需抽取10毫升血液就能收集循环肿瘤细胞（CTC）。这些CTC概括了相应肿瘤的分子异质性，因此可用作研究肿瘤生物学和生成新的患者来源模型的替代物。在此，我们讨论已建立的CTC衍生模型，尤其是在小细胞肺癌（SCLC）中的模型，强调与这些新型临床前工具相关的挑战和机遇。
