Adi F. Gazdar, MD, Fred R. Hirsch, MD, PhD, John D. Minna, MD

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Presentation transcript:

From Mice to Men and Back: An Assessment of Preclinical Model Systems for the Study of Lung Cancers Adi F. Gazdar, MD, Fred R. Hirsch, MD, PhD, John D. Minna, MD Journal of Thoracic Oncology Volume 11, Issue 3, Pages 287-299 (March 2016) DOI: 10.1016/j.jtho.2015.10.009 Copyright © 2015 International Association for the Study of Lung Cancer Terms and Conditions

Figure 1 Lung cancer cell lines. (A) Non–small cell lung cancer culture HCC1897, growing as flat adherent cells. (B) Small cell lung cancer culture, triple-knockout mouse model. Both mouse and human small cell lung cancer cultures usually grow as floating aggregates or true spheroids (as shown). The larger spheroids frequently develop necrotic or hollow centers. Journal of Thoracic Oncology 2016 11, 287-299DOI: (10.1016/j.jtho.2015.10.009) Copyright © 2015 International Association for the Study of Lung Cancer Terms and Conditions

Figure 2 Patient-derived xenografts of moderately differentiated squamous cell carcinoma. The histological appearances of the patient-derived xenografts are similar to those of the original lung cancer. Journal of Thoracic Oncology 2016 11, 287-299DOI: (10.1016/j.jtho.2015.10.009) Copyright © 2015 International Association for the Study of Lung Cancer Terms and Conditions

Figure 3 Typical Kras-driven genetically engineered mouse model for lung adenocarcinoma. The most striking feature is the massive alveolar cell hyperplasia. If the mice do not die of respiratory failure, adenomas may develop that progress to adenomas with dysplasia, adenocarcinoma in situ, and invasive carcinoma. Courtesy of James Kim, MD, PhD. Journal of Thoracic Oncology 2016 11, 287-299DOI: (10.1016/j.jtho.2015.10.009) Copyright © 2015 International Association for the Study of Lung Cancer Terms and Conditions

Figure 4 Genetically engineered triple-knockout mouse models for neuroendocrine lung cancers. (A) Early central lesion arising in a large bronchus. Both the in situ and invasive components are characteristic of large cell neuroendocrine carcinoma (LCNEC) with pseudoglandular formation. (B) Massive mediastinal spread of the small cell lung carcinoma (SCLC) component, even though corresponding intrapulmonary tumors are relatively small. (C) Mixed tumor with LCNEC (left) and SCLC (on right) components blending into each other. (D) Liver metastases with SCLC elements only, even though the primary tumor had both SCLC and LCNEC components. The SCLC component predominated in metastatic lesions, regardless of the histology of the corresponding lung tumors. (Reprinted from Gazdar et al.,37 with permission.) Journal of Thoracic Oncology 2016 11, 287-299DOI: (10.1016/j.jtho.2015.10.009) Copyright © 2015 International Association for the Study of Lung Cancer Terms and Conditions