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Published on: July 5, 2019
Microfluidic Arrays of Breast Tumor Spheroids for Drug Screening and Personalized Cancer Therapies
Elisabeth Prince1, Sina Kheiri2, Yihe Wang1
1Department of Chemistry, University of Toronto, 80 St. George St, Toronto, Ontario, M5P 2Y2, Canada.
Abstract:
One of the obstacles limiting progress in the development of effective cancer therapies is the shortage of preclinical models that capture the dynamic nature of tumor microenvironments. Interstitial flow strongly impacts tumor response to chemotherapy; however, conventional in vitro cancer models largely disregard this key feature. Here, a proof of principle microfluidic platform for the generation of large arrays of breast tumor spheroids that are grown under close-to-physiological flow in a biomimetic hydrogel is reported. This cancer spheroids-on-a-chip model is used for time- and labor-efficient studies of the effects of drug dose and supply rate on the chemosensitivity of breast tumor spheroids. The capability to grow large arrays of tumor spheroids from patient-derived cells of different breast cancer subtypes is shown, and the correlation between in vivo drug efficacy and on-chip spheroid drug response is demonstrated. The proposed platform can serve as an in vitro preclinical model for the development of personalized cancer therapies and effective screening of new anticancer drugs.
Insights
Developing advanced cancer models is crucial for effective therapies. This study introduces a microfluidic platform simulating tumor microenvironments to improve drug screening and personalized cancer treatment.
Area of Science:
- Oncology
- Biomedical Engineering
- Microfluidics
Background:
- Effective cancer therapies are hindered by a lack of preclinical models that accurately represent dynamic tumor microenvironments.
- Interstitial flow significantly influences tumor response to chemotherapy, a factor often overlooked in conventional in vitro models.
Purpose of the Study:
- To develop and validate a microfluidic platform for generating breast tumor spheroids under physiological flow conditions.
- To enable time- and labor-efficient studies on drug dose and supply rate effects on breast tumor spheroid chemosensitivity.
Main Methods:
- A microfluidic platform was engineered to create large arrays of breast tumor spheroids within a biomimetic hydrogel.
- Spheroids were cultured under controlled, near-physiological interstitial flow conditions.
- The platform was utilized to test drug efficacy using patient-derived cells from various breast cancer subtypes.
Main Results:
- The platform successfully generated numerous breast tumor spheroids under biomimetic flow.
- The study demonstrated the correlation between in vivo drug efficacy and the drug response observed in the on-chip spheroids.
- The model showed efficiency in assessing the impact of drug dose and delivery rate on chemosensitivity.
Conclusions:
- The developed microfluidic 'spheroids-on-a-chip' platform serves as a valuable in vitro preclinical model.
- This platform supports the development of personalized cancer therapies by utilizing patient-derived cells.
- It offers a robust system for the efficient screening of novel anticancer drugs.
