Table 1.

Biomimetic approaches to engineering tumors

		Advantages	Disadvantages
Single and multicellular tumor spheroids	Inch et al. (1970)8 Sutherland (1988)9 Helmlinger et al. (1997)10 Hirschhaeuser et al. (2010)11 Kondo et al. (2011)12 La Barbera et al. (2012)13 Seano et al. (2013)14	Recapitulate tumor heterogeneity More predictive than monolayer High-throughput Inexpensive	No immune or other cells of the tumor microenvironment No vasculature No self-assembly Forced microanatomy
Tumor organoids	Cheung et al. (2013)15	Display typical tumor histological characteristics High-throughput Cheap	No immune or other cells of the tumor microenvironment No vasculature
	Huang et al. (2015)16	Retain differentiation status, histo-architecture and phenotypic heterogeneity of primary tumor including patient tumors Retain patient-specific physiological changes High-throughput	No immune or other cells of the tumor microenvironment No vasculature Pancreatic progenitor cells plated on Matrigel
	Li et al. (2014)17	Long term viability Model diverse gastrointestinal malignancies from pancreas, stomach and colon in primary epithelial and mesenchymal organoid culture Oncogenic trans- formation in vitro Tumorigenicity after transplantation in vivo	No vasculature
Ex vivo tumor slice cultures	Merz et al. (2013)18 Gerlach et al. (2014)19 Chadwick et al. (2015)20	Preservation of the individual histopathology High-throughput	Explants’ blood vessels are isolated, not integrated into a surrounding network formed in vitro Explant viability depends on the explant origin Mostly applied to brain cultures
Cell sheet technology	Kushida et al. (1999)21	Preservation of the deposited ECM and cell-cell interactions Improved cell engraftment and tumor formation following subcutaneous mouse injection	No vasculature No self assembly Forced microanatomy
Microfluidic models	Ehsan et al. (2014)22	Vasculature present	Use of spheroids
Bioreactors	Ferranini et al (2013)23	Long term viability and histo-architecture of the tissue explants retained Tissue blood vessel integrity maintained	Not suitable for drug screening Not amenable for longitudinal microscopic imaging Explants’ blood vessels are isolated, not integrated into a surrounding network formed in vitro
	Domansky et al. (2010)24	High-throughput	Use of hepatocyte monocultures No vasculature
Self-assembly	Bazou et al.	Long term viability and histo-architecture of the tumor explant retained, including patient tumors Explants’ blood vessel system retained Explants’ blood vessels integrate into a surrounding network formed in vitro Long term maintenance of in vitro vascular network High-throughput Inexpensive	Size of the explant is limiting (≤ 0.5 mm) Vessel network requires ~7 days to establish