Leveraging and manufacturing in vitro multicellular spheroid-based tumor cell model as a preclinical tool for translating dysregulated tumor metabolism into clinical targets and biomarkers
Abstract The grand challenge now and in the near future for the pharmaceutical industry is how to efficiently improve R&D productivity. Currently, the approval rate of the entire clinical drug development process is extremely low, and the high attrition in the phase I clinical trial is up to 95%...
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| Format: | Article |
| Language: | English |
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SpringerOpen
2020-07-01
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| Series: | Bioresources and Bioprocessing |
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| Online Access: | http://link.springer.com/article/10.1186/s40643-020-00325-7 |
| _version_ | 1811342003048284160 |
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| author | Tong Wang Lin Wang Guan Wang Yingping Zhuang |
| author_facet | Tong Wang Lin Wang Guan Wang Yingping Zhuang |
| author_sort | Tong Wang |
| collection | DOAJ |
| description | Abstract The grand challenge now and in the near future for the pharmaceutical industry is how to efficiently improve R&D productivity. Currently, the approval rate of the entire clinical drug development process is extremely low, and the high attrition in the phase I clinical trial is up to 95%; 67% and 33% of all drugs that enter Phase II and Phase III clinical trials fail to transit into the next stage, respectively. To achieve a higher success rate in clinical trials, developing efficient drug screening method based on more in vivo like tumor tissue is an urgent need to predict the toxicity and efficacy of candidate drugs. In comparison to 2D planar tumor model, the 3D multicellular tumor spheroid (MTS) can better simulate the spatial structure, hypoxia and nutrient gradient, extracellular matrix (ECM) deposition and drug resistance mechanism of tumor in vivo. Thus, such model can be applied for high-throughput drug screening and evaluation, and also can be utilized to initiate a series of fundamental research areas regarding oncogenesis, tumor progression and invasion, pharmacokinetics, drug metabolism, gene therapy and immune mechanism. This review article discusses the abnormal metabolism of cancer cells and highlights the potential role of MTSs as being used as efficient preclinical models. Also, the key features and preparation protocols of MTSs as well as the tools and techniques used for their analysis were summarized and the application of 3D tumor spheroid in specific drug screening and in the elucidation of drug resistance mechanism was also provided. Despite the great knowledge gap within biological sciences and bioengineering, the grand blueprint for adaptable stirred-tank culture strategies for large-scale production of MTSs is envisioned. |
| first_indexed | 2024-04-13T19:03:28Z |
| format | Article |
| id | doaj.art-6f5129a9e89249719f16bc32bea3a680 |
| institution | Directory Open Access Journal |
| issn | 2197-4365 |
| language | English |
| last_indexed | 2024-04-13T19:03:28Z |
| publishDate | 2020-07-01 |
| publisher | SpringerOpen |
| record_format | Article |
| series | Bioresources and Bioprocessing |
| spelling | doaj.art-6f5129a9e89249719f16bc32bea3a6802022-12-22T02:34:02ZengSpringerOpenBioresources and Bioprocessing2197-43652020-07-017113410.1186/s40643-020-00325-7Leveraging and manufacturing in vitro multicellular spheroid-based tumor cell model as a preclinical tool for translating dysregulated tumor metabolism into clinical targets and biomarkersTong Wang0Lin Wang1Guan Wang2Yingping Zhuang3State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology (ECUST)State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology (ECUST)State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology (ECUST)State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology (ECUST)Abstract The grand challenge now and in the near future for the pharmaceutical industry is how to efficiently improve R&D productivity. Currently, the approval rate of the entire clinical drug development process is extremely low, and the high attrition in the phase I clinical trial is up to 95%; 67% and 33% of all drugs that enter Phase II and Phase III clinical trials fail to transit into the next stage, respectively. To achieve a higher success rate in clinical trials, developing efficient drug screening method based on more in vivo like tumor tissue is an urgent need to predict the toxicity and efficacy of candidate drugs. In comparison to 2D planar tumor model, the 3D multicellular tumor spheroid (MTS) can better simulate the spatial structure, hypoxia and nutrient gradient, extracellular matrix (ECM) deposition and drug resistance mechanism of tumor in vivo. Thus, such model can be applied for high-throughput drug screening and evaluation, and also can be utilized to initiate a series of fundamental research areas regarding oncogenesis, tumor progression and invasion, pharmacokinetics, drug metabolism, gene therapy and immune mechanism. This review article discusses the abnormal metabolism of cancer cells and highlights the potential role of MTSs as being used as efficient preclinical models. Also, the key features and preparation protocols of MTSs as well as the tools and techniques used for their analysis were summarized and the application of 3D tumor spheroid in specific drug screening and in the elucidation of drug resistance mechanism was also provided. Despite the great knowledge gap within biological sciences and bioengineering, the grand blueprint for adaptable stirred-tank culture strategies for large-scale production of MTSs is envisioned.http://link.springer.com/article/10.1186/s40643-020-00325-7Multicellular tumor spheroidsIn vitro modelsTumor metabolismPreclinical evaluationCancer therapyPrecision medicine |
| spellingShingle | Tong Wang Lin Wang Guan Wang Yingping Zhuang Leveraging and manufacturing in vitro multicellular spheroid-based tumor cell model as a preclinical tool for translating dysregulated tumor metabolism into clinical targets and biomarkers Bioresources and Bioprocessing Multicellular tumor spheroids In vitro models Tumor metabolism Preclinical evaluation Cancer therapy Precision medicine |
| title | Leveraging and manufacturing in vitro multicellular spheroid-based tumor cell model as a preclinical tool for translating dysregulated tumor metabolism into clinical targets and biomarkers |
| title_full | Leveraging and manufacturing in vitro multicellular spheroid-based tumor cell model as a preclinical tool for translating dysregulated tumor metabolism into clinical targets and biomarkers |
| title_fullStr | Leveraging and manufacturing in vitro multicellular spheroid-based tumor cell model as a preclinical tool for translating dysregulated tumor metabolism into clinical targets and biomarkers |
| title_full_unstemmed | Leveraging and manufacturing in vitro multicellular spheroid-based tumor cell model as a preclinical tool for translating dysregulated tumor metabolism into clinical targets and biomarkers |
| title_short | Leveraging and manufacturing in vitro multicellular spheroid-based tumor cell model as a preclinical tool for translating dysregulated tumor metabolism into clinical targets and biomarkers |
| title_sort | leveraging and manufacturing in vitro multicellular spheroid based tumor cell model as a preclinical tool for translating dysregulated tumor metabolism into clinical targets and biomarkers |
| topic | Multicellular tumor spheroids In vitro models Tumor metabolism Preclinical evaluation Cancer therapy Precision medicine |
| url | http://link.springer.com/article/10.1186/s40643-020-00325-7 |
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