Division of Hematology & Medical Oncology, Laura and Isaac Perlmutter Cancer Center, New York University Langone Medical Center, New York, NY, USA.
Oncogene. 2021 Apr;40(16):2817-2829. doi: 10.1038/s41388-021-01723-7. Epub 2021 Mar 11.
Lung squamous cell carcinoma (LUSC) represents a major subtype of non-small cell lung cancer with limited treatment options. Previous studies have elucidated the complex genetic landscape of LUSC and revealed multiple altered genes and pathways. However, in stark contrast to lung adenocarcinoma, few targetable driver mutations have been established so far and targeted therapies for LUSC remain unsuccessful. Immunotherapy has revolutionized LUSC treatment and is currently approved as the new standard of care. To gain a better understanding of the LUSC biology, improved modeling systems are urgently needed. Preclinical models, particularly those mimicking human disease with an intact tumor immune microenvironment, are an invaluable tool to study cancer development and evaluate new therapeutic targets. Here, we discuss recent advances in LUSC preclinical models, with a focus on genetically engineered mouse models (GEMMs) and organoids, in the context of evolving precision medicine and immunotherapy.
肺鳞状细胞癌(LUSC)是一种非小细胞肺癌的主要亚型,治疗选择有限。先前的研究阐明了 LUSC 复杂的遗传景观,并揭示了多个改变的基因和途径。然而,与肺腺癌形成鲜明对比的是,目前为止很少确定可靶向的驱动突变,LUSC 的靶向治疗仍然不成功。免疫疗法彻底改变了 LUSC 的治疗方法,目前被批准为新的治疗标准。为了更好地了解 LUSC 的生物学特性,迫切需要改进的建模系统。临床前模型,特别是那些模拟具有完整肿瘤免疫微环境的人类疾病的模型,是研究癌症发展和评估新治疗靶点的宝贵工具。在这里,我们讨论了 LUSC 临床前模型的最新进展,重点是基因工程小鼠模型(GEMMs)和类器官,以及不断发展的精准医学和免疫疗法的背景。