The application of personalized medicine to lung adenocarcinoma has resulted in new therapies based on specific oncogenic drivers that have improved patient outcomes. However, oncogene-defined subsets of patients exhibit a significant heterogeneity of response to these agents. Defining the factors that mediate the varied depth and duration of response are critical to developing new therapeutic strategies. While the examination of patient samples can provide important correlations, definitive mechanistic studies require the use of relevant preclinical models. Based on a large body of data, interactions between cancer cells and the surrounding tumor microenvironment, comprised of inflammatory, immune, and vascular cells, represent a critical determinant of therapeutic response. In this review, we focus on preclinical models that can be used to explore these interactions, identify new therapeutic targets, and test combination therapies. In particular, we will describe the use of implantable orthotopic immunocompetent models employing a panel of murine lung adenocarcinoma cell lines with oncogenic drivers common to human lung adenocarcinoma as a powerful system to develop new treatment approaches.
将个体化医疗应用于肺腺癌治疗，已催生出基于特定致癌驱动因子的新型疗法，显著改善了患者预后。然而，即使在同一致癌基因定义的亚组中，患者对这些药物的反应仍存在显著异质性。明确影响治疗反应深度和持续时间的调控因素，对开发新治疗策略至关重要。虽然临床样本分析能提供重要相关性证据，但确切的机制研究仍需借助相关临床前模型。大量研究表明，癌细胞与肿瘤微环境（包括炎症细胞、免疫细胞及血管细胞）间的相互作用是决定治疗反应的关键因素。本综述重点探讨可用于探索这些相互作用、识别新治疗靶点及测试联合疗法的临床前模型。特别地，我们将阐述利用一组携带人类肺腺癌常见致癌驱动基因的小鼠肺腺癌细胞系，构建可植入式原位免疫活性模型，作为开发新型治疗策略的强大研究体系。
Orthotopically Implanted Murine Lung Adenocarcinoma Cell Lines for Preclinical Investigations
肿瘤(癌症)患者之家