title: Genetic instability in the tumor microenvironment: a new look at an old neighbor.
abstract: The recent exponential increase in our knowledge of cellular and molecular mechanisms involved in carcinogenesis has largely failed to translate into new therapies and clinical practices. This lack of success may result in part from the fact that most studies focus on tumor cells as potential therapeutic targets and neglect the complex microenvironment that undergoes profound changes during tumor development. Furthermore, an unfortunate association of factors such as tumor genetic complexity, overestimation of biomarker and drug potentials, as well as a poor understanding of tumor microenvironment in diagnosis and prognosis leads to the current levels of treatment failure regarding a vast majority of cancer types. A growing body of evidence points to the importance of the functional diversity of immune and structural cells during tumor development. In this sense, the lack of technologies that would allow for molecular screening of individual stromal cell types poses a major challenge for the development of therapies targeting the tumor microenvironment. Progress in microenvironment genetic studies represents a formidable opportunity for the development of new selective drugs because stromal cells have lower mutation rates than malignant cells, and should prove to be good targets for therapy.
authors.affiliation: Laboratório de Interações Celulares, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Prédio de Ciências da Saúde - Cidade Universitária, Ilha do Fundão, A. Carlos Chagas, 373 - bloco F, sala 26, 21941-902, Rio de Janeiro, RJ, Brasil. palumbo@ufrj.br.|Programa de Carcinogênese Molecular, Instituto Nacional de Câncer José de Alencar Gomes da Silva, Rua André Cavalcanti, 37 - 6° andar - Centro, 20231-050, Rio de Janeiro, RJ, Brasil. palumbo@ufrj.br.
authors.forename: Antonio
authors.initials: A
authors.lastname: Palumbo
authors.affiliation: Programa de Carcinogênese Molecular, Instituto Nacional de Câncer José de Alencar Gomes da Silva, Rua André Cavalcanti, 37 - 6° andar - Centro, 20231-050, Rio de Janeiro, RJ, Brasil. natmeireles@gmail.com.
authors.forename: Nathalia de Oliveira Meireles
authors.initials: Nde O
authors.lastname: Da Costa
authors.affiliation: Programa de Carcinogênese Molecular, Instituto Nacional de Câncer José de Alencar Gomes da Silva, Rua André Cavalcanti, 37 - 6° andar - Centro, 20231-050, Rio de Janeiro, RJ, Brasil. mbonamino@inca.gov.br.|Fundação Oswaldo Cruz, Vice-presidência de Pesquisa e Laboratórios de Referência, Rio de Janeiro, Brasil, Av. Brasil, 4365 - Pavilhão Mourisco - Manguinhos, 21040-900, Rio de Janeiro, RJ, Brasil. mbonamino@inca.gov.br.
authors.forename: Martin Hernan
authors.initials: MH
authors.lastname: Bonamino
authors.affiliation: Programa de Carcinogênese Molecular, Instituto Nacional de Câncer José de Alencar Gomes da Silva, Rua André Cavalcanti, 37 - 6° andar - Centro, 20231-050, Rio de Janeiro, RJ, Brasil. lfrpinto@inca.gov.br.
authors.forename: Luis Felipe Ribeiro
authors.initials: LF
authors.lastname: Pinto
authors.affiliation: Laboratório de Interações Celulares, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Prédio de Ciências da Saúde - Cidade Universitária, Ilha do Fundão, A. Carlos Chagas, 373 - bloco F, sala 26, 21941-902, Rio de Janeiro, RJ, Brasil. luiz.nasciutti@histo.ufrj.br.
authors.forename: Luiz Eurico
authors.initials: LE
authors.lastname: Nasciutti
mesh_terms: D000818:Animals; D002450:Cell Communication / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D042822:Genomic Instability / Q000187:drug effects / Q000235:genetics; D006801:Humans; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000235:genetics* / Q000276:immunology / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D059016:Tumor Microenvironment / Q000235:genetics* / Q000276:immunology