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Published on: February 17, 2023
Advanced Cellular Models for Preclinical Drug Testing: From 2D Cultures to Organ-on-a-Chip Technology
Valentina Foglizzo1, Emiliano Cocco1, Serena Marchiò2,3
1Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
Abstract:
Cancer is a complex disease arising from a homeostatic imbalance of cell-intrinsic and microenvironment-related mechanisms. A multimodal approach to treat cancer that includes surgery, chemotherapy, and radiation therapy often fails in achieving tumor remission and produces unbearable side effects including secondary malignancies. Novel strategies have been implemented in the past decades in order to replace conventional chemotherapeutics with targeted, less toxic drugs. Up to now, scientists have relied on results achieved in animal research before proceeding to clinical trials. However, the high failure rate of targeted drugs in early phase trials leaves no doubt about the inadequacy of those models. In compliance with the need of reducing, and possibly replacing, animal research, studies have been conducted in vitro with advanced cellular models that more and more mimic the tumor in vivo. We will here review those methods that allow for the 3D reconstitution of the tumor and its microenvironment and the implementation of the organ-on-a-chip technology to study minimal organ units in disease progression. We will make specific reference to the usability of these systems as predictive cancer models and report on recent applications in high-throughput screenings of innovative and targeted drug compounds.
Insights
Advanced in vitro cancer models, including 3D tumor reconstructions and organ-on-a-chip technology, offer superior prediction of drug efficacy compared to traditional animal research. These novel methods reduce animal testing and improve targeted cancer therapy development.
Area of Science:
- Oncology
- Biotechnology
- Drug Discovery
Background:
- Cancer treatment faces challenges with conventional therapies leading to side effects and drug resistance.
- Current animal models for preclinical drug testing have a high failure rate, necessitating improved predictive models.
- There is a growing need to reduce and replace animal research in drug development.
Purpose of the Study:
- To review advanced in vitro methods for cancer research.
- To highlight the potential of 3D tumor and microenvironment models and organ-on-a-chip technology.
- To discuss the application of these models in predictive cancer research and high-throughput drug screening.
Main Methods:
- Review of in vitro advanced cellular models.
- Focus on 3D reconstitution of tumor and microenvironment.
- Integration of organ-on-a-chip technology for studying minimal organ units.
Main Results:
- Advanced cellular models increasingly mimic in vivo tumors.
- Organ-on-a-chip technology enables study of minimal organ units in disease progression.
- These systems show promise as predictive cancer models.
Conclusions:
- In vitro advanced cellular models offer a more accurate platform for cancer research.
- Organ-on-a-chip technology and 3D models are crucial for developing targeted cancer therapies.
- These methods enhance high-throughput screening of novel drug compounds and reduce reliance on animal models.
