Three Dimensional Tissue Models for Research in Oncology

Nietzer, Sarah; Dandekar, Gudrun; Wasik, Milena A.; Walles, Heike

doi:10.5772/33600

Cited by 2 publications

(3 citation statements)

References 40 publications

(69 reference statements)

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“…Cancer therapy is a rather young medical discipline which, from 1950's up to now has resulted in the approval of nearly 183 anti-cancer drugs [3,4]. It also poses an unprecedented challenge to big pharmaceutical industry since the costs for the development of a single anti-cancer drug can reach up to US$ 1 billion [5,6]. The process of drug development involves critical and systematic steps with many drawbacks and turnarounds.…”

Section: Introductionmentioning

confidence: 99%

“…The process of drug development involves critical and systematic steps with many drawbacks and turnarounds. It is estimated that per 10,000 compounds analyzed for different applications, only one reaches approval [6]. In the case of anticancer drugs, the attrition rates are even higher, since only 5% of substances passing clinical testing are later licensed and many others commercially available are later withdrawn from the market [7].…”

Section: Introductionmentioning

confidence: 99%

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Anti-Cancer Drug Validation: the Contribution of Tissue Engineered Models

Carvalho

Lima

Reis

et al. 2017

Stem Cell Rev and Rep

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Drug toxicity frequently goes concealed until clinical trials stage, which is the most challenging, dangerous and expensive stage of drug development. Both the cultures of cancer cells in traditional 2D assays and animal studies have limitations that cannot ever be unraveled by improvements in drug-testing protocols. A new generation of bioengineered tumors is now emerging in response to these limitations, with potential to transform drug screening by providing predictive models of tumors within their tissue context, for studies of drug safety and efficacy. Considering the NCI60, a panel of 60 cancer cell lines representative of 9 different cancer types: leukemia, lung, colorectal, central nervous system (CNS), melanoma, ovarian, renal, prostate and breast, we propose to review current "state of art" on the 9 cancer types specifically addressing the 3D tissue models that have been developed and used in drug discovery processes as an alternative to complement their study.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Anti-Cancer Drug Validation: the Contribution of Tissue Engineered Models

Carvalho

Lima

Reis

et al. 2017

Stem Cell Rev and Rep

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“…Although the flat and artificially stiff surfaces in two-dimensional monolayer cell culture are simple to set up, they are far from sufficient to emulate the physical and biochemical complexity and dynamics in vivo, where cells typically face a complex three-dimensional microenvironment, consisting of heterogeneous, fibrous networks of extracellular matrix (ECM) and other types of coexisting cells [6]. As such, three-dimensional models have been increasingly developed for modelling cancers [7] and testing therapeutics [8], as these models offer the potential to maximize the physiological relevance of in vitro cell culture, and better simulate the spatio-temporal gradient of cues for cell migration found in the native tissue context. Indeed, three-dimensional cancer models have shown numerous advantages in terms of recapitulating cancer malignancy in vitro.…”

Section: Introductionmentioning

confidence: 99%

Mechanistic adaptability of cancer cells strongly affects anti-migratory drug efficacy

Sun

Lim

Kurniawan

2014

J. R. Soc. Interface.

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Cancer metastasis involves the dissemination of cancer cells from the primary tumour site and is responsible for the majority of solid tumour-related mortality. Screening of anti-metastasis drugs often includes functional assays that examine cancer cell invasion inside a three-dimensional hydrogel that mimics the extracellular matrix (ECM). Here, we built a mechanically tuneable collagen hydrogel model to recapitulate cancer spreading into heterogeneous tumour stroma and monitored the three-dimensional invasion of highly malignant breast cancer cells, MDA-MB-231. Migration assays were carried out in the presence and the absence of drugs affecting four typical molecular mechanisms involved in cell migration, as well as under five ECMs with different biophysical properties. Strikingly, the effects of the drugs were observed to vary strongly with matrix mechanics and microarchitecture, despite the little dependence of the inherent cancer cell migration on the ECM condition. Specifically, cytoskeletal contractility-targeting drugs reduced migration speed in sparse gels, whereas migration in dense gels was retarded effectively by inhibiting proteolysis. The results corroborate the ability of cancer cells to switch their multiple invasion mechanisms depending on ECM condition, thus suggesting the importance of factoring in the biophysical properties of the ECM in anti-metastasis drug screenings.

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Three Dimensional Tissue Models for Research in Oncology

Cited by 2 publications

References 40 publications

Anti-Cancer Drug Validation: the Contribution of Tissue Engineered Models

Anti-Cancer Drug Validation: the Contribution of Tissue Engineered Models

Mechanistic adaptability of cancer cells strongly affects anti-migratory drug efficacy

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