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Engineering Breast Cancer On-chip-Moving Toward Subtype Specific Models
Carmen Moccia1, Kristina Haase1
1European Molecular Biology Laboratory, European Molecular Biology Laboratory Barcelona, Barcelona, Spain.
Abstract:
Breast cancer is the second leading cause of death among women worldwide, and while hormone receptor positive subtypes have a clear and effective treatment strategy, other subtypes, such as triple negative breast cancers, do not. Development of new drugs, antibodies, or immune targets requires significant re-consideration of current preclinical models, which frequently fail to mimic the nuances of patient-specific breast cancer subtypes. Each subtype, together with the expression of different markers, genetic and epigenetic profiles, presents a unique tumor microenvironment, which promotes tumor development and progression. For this reason, personalized treatments targeting components of the tumor microenvironment have been proposed to mitigate breast cancer progression, particularly for aggressive triple negative subtypes. To-date, animal models remain the gold standard for examining new therapeutic targets; however, there is room for in vitro tools to bridge the biological gap with humans. Tumor-on-chip technologies allow for precise control and examination of the tumor microenvironment and may add to the toolbox of current preclinical models. These new models include key aspects of the tumor microenvironment (stroma, vasculature and immune cells) which have been employed to understand metastases, multi-organ interactions, and, importantly, to evaluate drug efficacy and toxicity in humanized physiologic systems. This review provides insight into advanced in vitro tumor models specific to breast cancer, and discusses their potential and limitations for use as future preclinical patient-specific tools.
Insights
Advanced in vitro tumor models, like tumor-on-chip technology, offer promising patient-specific preclinical tools for breast cancer research, especially for hard-to-treat triple-negative subtypes.
Area of Science:
- Oncology
- Biotechnology
- Preclinical Research
Background:
- Breast cancer, particularly triple-negative subtypes, lacks effective treatment strategies and adequate preclinical models.
- Tumor microenvironment complexity hinders the development of targeted therapies for diverse breast cancer subtypes.
- Current animal models often fail to replicate patient-specific breast cancer nuances.
Purpose of the Study:
- To review advanced in vitro tumor models for breast cancer research.
- To discuss the potential and limitations of these models as patient-specific preclinical tools.
- To highlight tumor-on-chip technologies for studying the tumor microenvironment.
Main Methods:
- Review of current literature on in vitro tumor models, focusing on breast cancer applications.
- Analysis of tumor-on-chip technologies incorporating stroma, vasculature, and immune cells.
- Evaluation of models for studying metastasis, multi-organ interactions, and drug efficacy/toxicity.
Main Results:
- In vitro tumor models, especially tumor-on-chip systems, provide precise control over the tumor microenvironment.
- These advanced models can better mimic human physiology and patient-specific tumor characteristics.
- Tumor-on-chip technologies show potential in evaluating drug efficacy and toxicity in humanized systems.
Conclusions:
- Advanced in vitro tumor models are crucial for bridging the gap between current preclinical limitations and human biology.
- Tumor-on-chip technologies represent a significant advancement in breast cancer preclinical research.
- These models offer a promising avenue for developing personalized treatments, particularly for aggressive breast cancer subtypes.
