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Critical Reviews™ in Therapeutic Drug Carrier Systems
Fator do impacto: 2.9 FI de cinco anos: 3.72 SJR: 0.736 SNIP: 0.818 CiteScore™: 4.6

ISSN Imprimir: 0743-4863
ISSN On-line: 2162-660X

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Critical Reviews™ in Therapeutic Drug Carrier Systems

DOI: 10.1615/CritRevTherDrugCarrierSyst.2017018042
pages 185-208

Three- and Four-Dimensional Spheroid and FiSS Tumoroid Cultures: Platforms for Drug Discovery and Development and Translational Research

R. R. Nair
Center for Research and Education in Nanobioengineering, University of South Florida, Tampa, FL 33612, USA; Departments of Internal Medicine, University of South Florida, Tampa, FL 33612, USA; Transgenex Nanobiotech Inc., Tampa, FL 33612, USA
S. Padhee
Center for Research and Education in Nanobioengineering, University of South Florida, Tampa, FL 33612, USA; Departments of Internal Medicine, University of South Florida, Tampa, FL 33612, USA; Transgenex Nanobiotech Inc., Tampa, FL 33612, USA; Department of Molecular Medicine, University of South Florida, Tampa, FL 33612, USA
T. Das
Department of Molecular Medicine, University of South Florida, Tampa, FL 33612, USA
R. Green
Center for Research and Education in Nanobioengineering, University of South Florida, Tampa, FL 33612, USA; Department of Molecular Medicine, University of South Florida, Tampa, FL 33612, USA
M. Howell
Center for Research and Education in Nanobioengineering, University of South Florida, Tampa, FL 33612, USA; Department of Molecular Medicine, University of South Florida, Tampa, FL 33612, USA
S. S. Mohapatra
Center for Research and Education in Nanobioengineering, University of South Florida, Tampa, FL 33612, USA; Departments of Internal Medicine, University of South Florida, Tampa, FL 33612, USA; James A. Haley VA Hospital, Tampa, FL, 33612, USA
Subhra Mohapatra
Center for Research and Education in Nanobioengineering, University of South Florida, Tampa, FL 33612, USA; Department of Molecular Medicine, University of South Florida, Tampa, FL 33612, USA; James A. Haley VA Hospital, Tampa, FL, 33612, USA

RESUMO

There have been remarkable improvements in our understanding of cancer biology. However, therapeutic improvements, with a few exceptions, have been minimal. Also, significant challenges remain in translating fundamental discoveries in cancer biology and genetics into effective drugs and cures. Traditional two-dimensional monolayer cell cultures lack predictive value, resulting in a >90% failure rate of compounds in clinical trials. A developing cancer is a symbiotic tissue consisting of cancer cells, including cancer stem cells (CSCs), and cohabitating with the components of its environment to form a tumor microenvironment (TME) niche. Throughout the process of tumorigenesis, ubiquitous autocrine and paracrine signaling between the cellular and noncellular components of the TME dictates the milieu and structure of this niche. Arising out of such interactions are the cancer cell's phenotypic characteristics, such as stemness, epithelial mesenchymal transformation (EMT), and drug resistance which in turn greatly affect the response of these cells to drug therapy. For these reasons, in order to delineate the mechanism of tumorigenesis and in the process discover drugs that will have greatest impact on tumor growth, it becomes imperative to study the cancer cell in context of its microenvironment. In the present review, we enumerate the advantages of three- and four-dimensional (3D and 4D) cell cultures and describe the various cell culture platforms that are being used to study tumorigenesis in vitro. These culture systems will not only aid in the study of tumor progression complexities in a cost-effective and rapid manner; they also are expected to facilitate the discovery and delivery of therapeutic regimens that will have more success making it to the clinic.


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