title: Modeling lung cancer evolution and preclinical response by orthotopic mouse allografts.
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.
authors.affiliation: Experimental Oncology, Molecular Oncology Programme, Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid, Spain.
authors.forename: Chiara
authors.initials: C
authors.lastname: Ambrogio
authors.affiliation: Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Carmona
authors.affiliation: Department of Pathology, Hospital Universitari de Bellvitge, Barcelona, Spain.
authors.forename: August
authors.initials: A
authors.lastname: Vidal
authors.affiliation: Department of Genetics, Biology and Biochemistry, Molecular Biotechnology Center, University of Torino, Torino, Italy.
authors.forename: Mattia
authors.initials: M
authors.lastname: Falcone
authors.affiliation: Experimental Oncology, Molecular Oncology Programme, Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid, Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: Nieto
authors.affiliation: Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain.
authors.forename: Octavio A
authors.initials: OA
authors.lastname: Romero
authors.affiliation: Translational Research Laboratory, Catalan Institute of Oncology, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Puertas
authors.affiliation: Translational Research Laboratory, Catalan Institute of Oncology, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Vizoso
authors.affiliation: Department of Medical Oncology, Catalan Institute of Oncology, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain.
authors.forename: Ernest
authors.initials: E
authors.lastname: Nadal
authors.affiliation: Department of Molecular Biotechnology and Health Sciences, Center for Experimental Research and Medical Studies (CERMS), University of Torino, Torino, Italy.
authors.forename: Teresa
authors.initials: T
authors.lastname: Poggio
authors.affiliation: Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Sánchez-Céspedes
authors.affiliation: Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain. Department of Physiological Sciences II, School of Medicine, University of Barcelona, Barcelona, Catalonia, Spain. Institucio Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Catalonia, Spain.
authors.forename: Manel
authors.initials: M
authors.lastname: Esteller
authors.affiliation: Molecular Imaging Unit, Biotechnology Programme, Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid, Spain.
authors.forename: Francisca
authors.initials: F
authors.lastname: Mulero
authors.affiliation: Department of Molecular Biotechnology and Health Sciences, Center for Experimental Research and Medical Studies (CERMS), University of Torino, Torino, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Voena
authors.affiliation: Department of Molecular Biotechnology and Health Sciences, Center for Experimental Research and Medical Studies (CERMS), University of Torino, Torino, Italy. Department of Pathology, Harvard Medical School, Boston Children's Hospital, Boston, Massachusetts.
authors.forename: Roberto
authors.initials: R
authors.lastname: Chiarle
authors.affiliation: Experimental Oncology, Molecular Oncology Programme, Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid, Spain.
authors.forename: Mariano
authors.initials: M
authors.lastname: Barbacid
authors.affiliation: Experimental Oncology, Molecular Oncology Programme, Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid, Spain. dsantamaria@cnio.es avillanueva@iconcologia.net.
authors.forename: David
authors.initials: D
authors.lastname: Santamaría
authors.affiliation: Translational Research Laboratory, Catalan Institute of Oncology, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain. XenOPAT S.L., Business Bioincubator, Bellvitge Health Science Campus, Barcelona, Spain. dsantamaria@cnio.es avillanueva@iconcologia.net.
authors.forename: Alberto
authors.initials: A
authors.lastname: Villanueva
mesh_terms: D064591:Allografts / Q000187:drug effects / Q000473:pathology; D000818:Animals; D005075:Biological Evolution; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D051379:Mice; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology