title: Increased complexity in carcinomas: Analyzing and modeling the interaction of human cancer cells with their microenvironment.
abstract: Solid cancers are not simple accumulations of malignant tumor cells but rather represent complex organ-like structures. Despite a more chaotic general appearance as compared to the highly organized setup of healthy tissues, cancers still show highly differentiated structures and a close interaction with and dependency on the interwoven connective tissue. This complexity within cancers is not known in detail at the molecular level so far. The first part of this article will shortly describe the technology and strategies to quantify and dissect the heterogeneity in human solid cancers. Moreover, there is urgent need to better understand human cancer biology since the development of novel anti-cancer drugs is far from being efficient, predominantly due to the scarcity of predictive preclinical models. Hence, in vivo and in vitro models were developed, which better recapitulate the complexity of human cancers, by their intrinsic three-dimensional nature and the cellular heterogeneity and allow functional intervention for hypothesis testing. Therefore, in the second part 3D in vitro cancer models are presented that analyze and depict the heterogeneity in human cancers. Advantages and drawbacks of each model are highlighted and their suitability to preclinical drug testing is discussed.
authors: Institute of Medical Genetics, Medical University of Vienna, Währinger Straße 10, A-1090 Vienna, Austria.
authors: Mira
authors: M
authors: Stadler
authors: Institute of Medical Genetics, Medical University of Vienna, Währinger Straße 10, A-1090 Vienna, Austria.
authors: Stefanie
authors: S
authors: Walter
authors: Institute of Medical Genetics, Medical University of Vienna, Währinger Straße 10, A-1090 Vienna, Austria.
authors: Angelika
authors: A
authors: Walzl
authors: Institute of Medical Genetics, Medical University of Vienna, Währinger Straße 10, A-1090 Vienna, Austria.
authors: Nina
authors: N
authors: Kramer
authors: Institute of Medical Genetics, Medical University of Vienna, Währinger Straße 10, A-1090 Vienna, Austria.
authors: Christine
authors: C
authors: Unger
authors: Institute of Medical Genetics, Medical University of Vienna, Währinger Straße 10, A-1090 Vienna, Austria.
authors: Martin
authors: M
authors: Scherzer
authors: Institute of Medical Genetics, Medical University of Vienna, Währinger Straße 10, A-1090 Vienna, Austria.
authors: Daniela
authors: D
authors: Unterleuthner
authors: Institute of Medical Genetics, Medical University of Vienna, Währinger Straße 10, A-1090 Vienna, Austria.
authors: Markus
authors: M
authors: Hengstschläger
authors: Institute of Pathology, Medical University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria.
authors: Georg
authors: G
authors: Krupitza
authors: Institute of Medical Genetics, Medical University of Vienna, Währinger Straße 10, A-1090 Vienna, Austria. Electronic address: helmut.dolznig@meduniwien.ac.at.
authors: Helmut
authors: H
authors: Dolznig
mesh_terms: D000818:Animals; D002277:Carcinoma / Q000209:etiology / Q000378:metabolism* / Q000473:pathology*; D002450:Cell Communication / Q000235:genetics; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008954:Models, Biological; D018874:Spheroids, Cellular; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology; D046509:Tissue Culture Techniques; D014407:Tumor Cells, Cultured; D059016:Tumor Microenvironment / Q000235:genetics
keywords: 3D; Cancer heterogeneity; Drug development; Spheroid; Tumor stroma