skip to main content
Idioma:

Three-dimensional models of cancer for pharmacology and cancer cell biology: Capturing tumor complexity in vitro/ex vivo

Hickman, John A. ; Graeser, Ralph ; de Hoogt, Ronald ; Vidic, Suzana ; Brito, Catarina ; Gutekunst, Matthias ; van der Kuip, Heiko ; IMI PREDECT consortium

Biotechnology journal, 2014-09, Vol.9 (9), p.1115-1128 [Periódico revisado por pares]

Weinheim: WILEY-VCH Verlag

Texto completo disponível

Citações Citado por
  • Título:
    Three-dimensional models of cancer for pharmacology and cancer cell biology: Capturing tumor complexity in vitro/ex vivo
  • Autor: Hickman, John A. ; Graeser, Ralph ; de Hoogt, Ronald ; Vidic, Suzana ; Brito, Catarina ; Gutekunst, Matthias ; van der Kuip, Heiko ; IMI PREDECT consortium
  • Assuntos: 3D models ; Animals ; Bioreactors ; Cancer ; Cell Biology ; Cell Culture Techniques - methods ; Drug discovery ; Humans ; In Vitro Techniques - methods ; Models, Biological ; Neoplasms - pathology ; Tissue slices
  • É parte de: Biotechnology journal, 2014-09, Vol.9 (9), p.1115-1128
  • Notas: EFPIA
    Innovative Medicines Initiative Joint Undertaking - No. 11518
    istex:D728CD818E347F836BDFB339E3278A10897CF23B
    ArticleID:BIOT201300492
    ark:/67375/WNG-B1HW56K8-W
    European Union's Seventh Framework Programme - No. FP7/2007-2013
    ObjectType-Article-2
    SourceType-Scholarly Journals-1
    ObjectType-Feature-3
    content type line 23
    ObjectType-Review-1
    ObjectType-Feature-1
  • Descrição: Cancers are complex and heterogeneous pathological “organs” in a dynamic interplay with their host. Models of human cancer in vitro, used in cancer biology and drug discovery, are generally highly reductionist. These cancer models do not incorporate complexity or heterogeneity. This raises the question as to whether the cancer models' biochemical circuitry (not their genome) represents, with sufficient fidelity, a tumor in situ. Around 95% of new anticancer drugs eventually fail in clinical trial, despite robust indications of activity in existing in vitro pre‐clinical models. Innovative models are required that better capture tumor biology. An important feature of all tissues, and tumors, is that cells grow in three dimensions. Advances in generating and characterizing simple and complex (with added stromal components) three‐dimensional in vitro models (3D models) are reviewed in this article. The application of stirred bioreactors to permit both scale‐up/scale‐down of these cancer models and, importantly, methods to permit controlled changes in environment (pH, nutrients, and oxygen) are also described. The challenges of generating thin tumor slices, their utility, and potential advantages and disadvantages are discussed. These in vitro/ex vivo models represent a distinct move to capture the realities of tumor biology in situ, but significant characterization work still remains to be done in order to show that their biochemical circuitry accurately reflects that of a tumor. This article reviews the current status of in vitro/ex vivo models for human cancer. It provides a short historical view and also highlights the pros and cons of different cultivation systems ranging from simplistic cell line based 2D mono‐ and co‐cultures over more complex 3D mono‐ and co‐cultures and sophisticated bioreactors to precision‐cut organotypic tissue slices. The article also addresses the rather provocative question of how any model may be “validated” sufficiently well so that it may be incorporated into mainstream activities not only relating to drug discovery but also to the study of tumor biology.
  • Editor: Weinheim: WILEY-VCH Verlag
  • Idioma: Inglês
Links
Voltar para lista de resultados

  • Realização: ABCD-USP USP   Logos de Redes Sociais: Freepik

Buscando em bases de dados remotas. Favor aguardar.