Cancer evolution is a process that is still poorly understood because of the lack of versatile in vivo longitudinal studies. By generating murine non-small cell lung cancer (NSCLC) orthoallobanks and paired primary cell lines, we provide a detailed description of an in vivo, time-dependent cancer malignization process. We identify the acquisition of metastatic dissemination potential, the selection of co-driver mutations, and the appearance of naturally occurring intratumor heterogeneity, thus recapitulating the stochastic nature of human cancer development. This approach combines the robustness of genetically engineered cancer models with the flexibility of allograft methodology. We have applied this tool for the preclinical evaluation of therapeutic approaches. This system can be implemented to improve the design of future treatments for patients with NSCLC.

Modeling lung cancer evolution and preclinical response by orthotopic mouse allografts

Ambrogio, Chiara;Poggio, Teresa;Voena, Claudia;Chiarle, Roberto;
2014-01-01

Abstract

Cancer evolution is a process that is still poorly understood because of the lack of versatile in vivo longitudinal studies. By generating murine non-small cell lung cancer (NSCLC) orthoallobanks and paired primary cell lines, we provide a detailed description of an in vivo, time-dependent cancer malignization process. We identify the acquisition of metastatic dissemination potential, the selection of co-driver mutations, and the appearance of naturally occurring intratumor heterogeneity, thus recapitulating the stochastic nature of human cancer development. This approach combines the robustness of genetically engineered cancer models with the flexibility of allograft methodology. We have applied this tool for the preclinical evaluation of therapeutic approaches. This system can be implemented to improve the design of future treatments for patients with NSCLC.
2014
74
21
5978
5988
http://cancerres.aacrjournals.org/content/74/21/5978.long
Allografts; Animals; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Disease Models, Animal; Humans; Lung Neoplasms; Mice; Neoplasms, Experimental; Biological Evolution; Oncology; Cancer Research
Ambrogio, Chiara*; Carmona, Francisco J.; Vidal, August; Falcone, Mattia; Nieto, Patricia; Romero, Octavio A.; Puertas, Sara; Vizoso, Miguel; Nadal, Ernest; Poggio, Teresa; Sánchez-Céspedes, Montserrat; Esteller, Manel; Mulero, Francisca; Voena, Claudia; Chiarle, Roberto; Barbacid, Mariano; Santamaría, David; Villanueva, Alberto
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/1688756
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