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A Novel Stromal Fibroblast-Modulated 3D Tumor Spheroid Model for Studying Tumor-Stroma Interaction and Drug Discovery
Published on: February 28, 2020
Anticancer drug discovery using multicellular tumor spheroid models
Michele Zanoni1, Sara Pignatta1, Chiara Arienti1
1a Biosciences Laboratory , Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS , Meldola , Italy.
Introduction:
Despite the increasing financial outlay on cancer research and drug discovery, many advanced cancers remain incurable. One possible strategy for increasing the approval rate of new anticancer drugs for use in clinical practice could be represented by three-dimensional (3D) tumor models on which to perform in vitro drug screening. There is a general consensus among the scientific community that 3D tumor models more closely recapitulate the complexity of tumor tissue architecture and biology than bi-dimensional cell cultures. In a 3D context, cells are connected to each other through tissue junctions and show proliferative and metabolic gradients that resemble the intricate milieu of organs and tumors. Areas covered: The present review focuses on available techniques for generating tumor spheroids and discusses current and future applications in the field of drug discovery. The article is based on literature obtained from PubMed. Expert opinion: Given the relative simplicity of spheroid models with respect to clinical tumors, we must be careful not to overestimate the reliability of their drug-response prediction capacity. The next challenge is to combine our knowledge of co-culture methodologies with high-content imaging and advanced microfluidic technologies to improve the readout and biomimetic potential of spheroid-based models.
Insights
Three-dimensional (3D) tumor models offer a more realistic in vitro drug screening platform than traditional 2D cultures. While promising for cancer drug discovery, their predictive capacity requires further enhancement with advanced technologies.
Area of Science:
- Oncology
- Drug Discovery
- Biotechnology
Background:
- Advanced cancers remain incurable despite significant investment in research.
- Traditional 2D cell cultures do not fully replicate tumor complexity.
- Three-dimensional (3D) tumor models offer a more biologically relevant in vitro system.
Purpose of the Study:
- To review techniques for generating tumor spheroids.
- To discuss current and future applications of 3D tumor models in drug discovery.
- To highlight the potential of 3D models in improving anticancer drug approval rates.
Main Methods:
- Literature review of PubMed-indexed articles.
- Focus on techniques for generating tumor spheroids.
- Analysis of current and future applications in drug discovery.
Main Results:
- 3D tumor models, such as spheroids, better mimic tumor architecture and cellular gradients than 2D cultures.
- These models provide a more accurate in vitro environment for drug screening.
- The review covers spheroid generation techniques and their utility in drug discovery.
Conclusions:
- 3D tumor models show promise for enhancing anticancer drug discovery and clinical translation.
- Caution is advised against overestimating the predictive power of current spheroid models.
- Future advancements require integrating co-culture, high-content imaging, and microfluidics to improve biomimicry and readout accuracy.
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