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Advancing cancer therapeutics: Integrating scalable 3D cancer models, extracellular vesicles, and omics for enhanced
Pedro P Gonçalves1, Cláudia L da Silva1, Nuno Bernardes1
1Department of Bioengineering and iBB - Institute for Bioengineering and Biosciences at Instituto Superior Técnico, Universidade de Lisboa, Lisboa, Portugal; Associate Laboratory i4HB - Institute for Health and Bioeconomy at Instituto Superior Técnico, Universidade de Lisboa, Lisboa, Portugal.
Abstract:
Cancer remains as one of the highest challenges to human health. However, anticancer drugs exhibit one of the highest attrition rates compared to other therapeutic interventions. In part, this can be attributed to a prevalent use of in vitro models with limited recapitulative potential of the in vivo settings. Three dimensional (3D) models, such as tumor spheroids and organoids, offer many research opportunities to address the urgent need in developing models capable to more accurately mimic cancer biology and drug resistance profiles. However, their wide adoption in high-throughput pre-clinical studies is dependent on scalable manufacturing to support large-scale therapeutic drug screenings and multi-omic approaches for their comprehensive cellular and molecular characterization. Extracellular vesicles (EVs), which have been emerging as promising drug delivery systems (DDS), stand to significantly benefit from such screenings conducted in realistic cancer models. Furthermore, the integration of these nanomedicines with 3D cancer models and omics profiling holds the potential to deepen our understanding of EV-mediated anticancer effects. In this chapter, we provide an overview of the existing 3D models used in cancer research, namely spheroids and organoids, the innovations in their scalable production and discuss how omics can facilitate the implementation of these models at different stages of drug testing. We also explore how EVs can advance drug delivery in cancer therapies and how the synergy between 3D cancer models and omics approaches can benefit in this process.
Insights
Three dimensional (3D) cancer models like spheroids and organoids improve drug screening accuracy. Integrating these models with omics profiling and extracellular vesicles (EVs) enhances anticancer drug development and delivery.
Area of Science:
- Oncology
- Biotechnology
- Drug Discovery
Background:
- Anticancer drug development faces high attrition rates due to limitations of traditional in vitro models.
- Three dimensional (3D) models, including tumor spheroids and organoids, offer improved recapitulation of in vivo cancer biology and drug resistance.
- Scalable manufacturing and comprehensive characterization are crucial for widespread adoption of 3D cancer models in preclinical studies.
Purpose of the Study:
- To review current 3D cancer models (spheroids, organoids) and innovations in their scalable production.
- To discuss the role of omics technologies in facilitating 3D model implementation for drug testing.
- To explore the potential of extracellular vesicles (EVs) as drug delivery systems (DDS) in cancer therapy and their synergy with 3D models and omics.
Main Methods:
- Overview of existing 3D cancer models (spheroids, organoids).
- Discussion of scalable manufacturing techniques for 3D models.
- Exploration of multi-omic approaches for 3D model characterization.
- Review of extracellular vesicles (EVs) as drug delivery systems (DDS).
Main Results:
- 3D models show promise in mimicking cancer biology and drug resistance more accurately than 2D models.
- Scalable production methods are advancing the use of 3D models in high-throughput screening.
- Omics profiling provides deep molecular insights into 3D models, aiding drug testing.
- EVs combined with 3D models and omics can enhance understanding of anticancer effects and drug delivery.
Conclusions:
- 3D cancer models, particularly spheroids and organoids, are vital for improving preclinical drug screening.
- Scalable manufacturing and omics integration are key to realizing the full potential of these advanced cancer models.
- The synergy between 3D models, omics, and extracellular vesicles offers a promising avenue for developing effective cancer therapies and drug delivery systems.
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