In Vitro Cancer Models: A Closer Look at Limitations on Translation
Abstract
:1. Introduction
2. 3D Cancer Models: Product Segments, Commercial Tools, Prototypes, and Patents
2.1. Surfaces and 3D Culture Plates
2.2. Scaffolds/Matrices
2.3. Patient-Derived and Cell Line-Based Assays/Services, Prototypes
2.4. Microfluidic Platforms
2.5. In Vitro Cancer Models: Patents
3. Gap Analysis: Limitations and Challenges of Existing Models
- The hierarchical heterogeneous structure of cancer results in phenotypic and genotypic diversities among the subpopulations of cancer cells. They are not possible to recapitulate in clinical models to date. The reductionist approaches to cancer modelling and the anti-systematic method of therapeutic screening are potent clinical failure recipes [93].
- There are differences between the biology of the model system and the context of the human body. For instance, tumors generally grow faster in laboratory animals or in vitro models than in humans [94].
- The discrepancy between site and stage of the disease in the preclinical model; for example, the subcutaneous tumor xenografts do not mimic the location and setting of the patient’s tumor. Therefore, the experimental therapeutic molecule fails to elicit the desired response at the pre-validated dose concentration [95].
- The inherited constraint of mimicking the advanced disease stage using commonly available cell lines, using more aggressive metastatic variants, such as MDA-MB 231/LM2-4 (triple-negative breast cancer cell line of human into immunodeficient mice (SCID)), to screen the FDA approved anticancer therapeutic Sunitinib, as the therapeutic for advanced metastatic breast cancer, also fails to elicit any response in mono or combination therapy [96].
- The introduction of immune therapy offers a logical approach to overcome the limitations mentioned above and exhibits promising results in treating breast, melanoma, urogenital or non-small cell lung cancers [97]. For instance, Keytruda is a humanized antibody that has received FDA approval as an immune therapeutic agent in the treatment of melanoma, head and neck cancer, and lung cancer patients [98]. However, in these success stories, little consideration is paid to the systematic or local compensatory immune–non-immune response mechanism, the cellular immune composition of site-directed tissues, the oxidation-reduction profile against checkpoint inhibitions, host immune–non-immune response, and adverse side-effects [99,100,101,102,103,104,105]. The systematic insight investigation of the mechanisms of these interdependent pathways and acute inflammatory and effective immune responses must be considered for more effective cancer immune therapy.
- A closer examination of detailed data spanning several decades reveals that persistent injuries, chronic infections, or inflammations cause genetic changes at site-specific tissues, increasing the risk of cancer, particularly in the elderly [102].
4. Concluding Remarks and Future Perspectives
Author Contributions
Funding
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Commercial Products | Marketed by | Features | Limitations | References |
---|---|---|---|---|
AggreWell™ | STEMCELL™ Technologies |
|
| [19] |
Corning® Spheroid Microplates | Corning® |
| [20] | |
CELLSTAR® Cell-Repellent Surface | Greiner Bio-One |
| [21] | |
NanoShuttle™-PL |
| |||
Lipidure®-COAT plates | AMS Biotechnology |
| [22] |
Commercial Products | Marketed by | Features | References |
---|---|---|---|
Alvetex® | AMS Biotechnology |
| [23] |
Biogelx™-S | BIOGELX™ |
| [24] |
BiogelxTM-RGD, BiogelxTM-IKVAV, BiogelxTM-YIGSR and BiogelxTM-GFOGER |
| ||
Matrigel® and PuraMatrix™ | Corning® |
| [20] |
CytoSoft® Rigidity plates | Advanced BioMatrix |
| [25] |
HyStem® | Sigma-Aldrich® |
| [26] |
MaxGel™ |
| [27] | |
TrueGel3D™ |
| [28] | |
Millicoat™ |
| [29] | |
MAPTrix™ | Kollodis BioSciences, Inc. |
| [30] |
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Share and Cite
Antunes, N.; Kundu, B.; Kundu, S.C.; Reis, R.L.; Correlo, V. In Vitro Cancer Models: A Closer Look at Limitations on Translation. Bioengineering 2022, 9, 166. https://doi.org/10.3390/bioengineering9040166
Antunes N, Kundu B, Kundu SC, Reis RL, Correlo V. In Vitro Cancer Models: A Closer Look at Limitations on Translation. Bioengineering. 2022; 9(4):166. https://doi.org/10.3390/bioengineering9040166
Chicago/Turabian StyleAntunes, Nina, Banani Kundu, Subhas C. Kundu, Rui L. Reis, and Vítor Correlo. 2022. "In Vitro Cancer Models: A Closer Look at Limitations on Translation" Bioengineering 9, no. 4: 166. https://doi.org/10.3390/bioengineering9040166