Lorz Corina, Oteo Marta, Santos Mirentxu
Molecular Oncology Unit (CIEMAT), Institute of Biomedical Research, University Hospital "12 de Octubre", CIBERONC, 28040 Madrid, Spain.
Biomedical Applications and Pharmacokinetics Unit (CIEMAT), 28040 Madrid, Spain.
Cancers (Basel). 2020 Dec 22;13(1):14. doi: 10.3390/cancers13010014.
Neuroendocrine lung tumors comprise a range of malignancies that extend from benign tumorlets to the most prevalent and aggressive Small Cell Lung Carcinoma (SCLC). They also include low-grade Typical Carcinoids (TC), intermediate-grade Atypical Carcinoids (AC) and high-grade Large Cell Neuroendocrine Carcinoma (LCNEC). Optimal treatment options have not been adequately established: surgical resection when possible is the choice for AC and TC, and for SCLC chemotherapy and very recently, immune checkpoint inhibitors. Some mouse models have been generated based on the molecular alterations identified in genomic analyses of human tumors. With the exception of SCLC, there is a limited availability of (preclinical) models making their development an unmet need for the understanding of the molecular mechanisms underlying these diseases. For SCLC, these models are crucial for translational research and novel drug testing, given the paucity of human material from surgery. The lack of early detection systems for lung cancer point them out as suitable frameworks for the identification of biomarkers at the initial stages of tumor development and for testing molecular imaging methods based on somatostatin receptors. Here, we review the relevant models reported to date, their impact on the understanding of the biology of the tumor subtypes and their relationships, as well as the effect of the analyses of the genetic landscape of the human tumors and molecular imaging tools in their development.
神经内分泌性肺肿瘤包括一系列恶性肿瘤，范围从良性微瘤到最常见且侵袭性最强的小细胞肺癌（SCLC）。它们还包括低级别典型类癌（TC）、中级别非典型类癌（AC）和高级别大细胞神经内分泌癌（LCNEC）。尚未充分确立最佳治疗方案：对于AC和TC，可能的话手术切除是首选；对于SCLC，则是化疗，以及最近的免疫检查点抑制剂。基于在人类肿瘤基因组分析中确定的分子改变，已经建立了一些小鼠模型。除SCLC外，（临床前）模型的可用性有限，这使得它们的开发成为理解这些疾病潜在分子机制的未满足需求。对于SCLC，鉴于手术获取的人体材料匮乏，这些模型对于转化研究和新药测试至关重要。肺癌缺乏早期检测系统，这表明它们是在肿瘤发展初期识别生物标志物以及测试基于生长抑素受体的分子成像方法的合适框架。在此，我们综述了迄今为止报道的相关模型、它们对理解肿瘤亚型生物学及其关系的影响，以及对人类肿瘤遗传图谱的分析和分子成像工具在其开发中的作用。
