Multiplexed drug testing of tumor slices using a microfluidic platform
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Abstract
Current methods to assess the drug response of individual human cancers are often inaccurate, costly, or slow. Functional approaches that rapidly and directly assess the response of patient cancer tissue to drugs or small molecules offer a promising way to improve drug testing, and have the potential to identify the best therapy for individual patients. We developed a digitally manufactured microfluidic platform for multiplexed drug testing of intact cancer slice cultures, and demonstrate the use of this platform to evaluate drug responses in slice cultures from human glioma xenografts and patient tumor biopsies. This approach retains much of the tissue microenvironment and can provide results rapidly enough, within days of surgery, to guide the choice of effective initial therapies. Our results establish a useful preclinical platform for cancer drug testing and development with the potential to improve cancer personalized medicine.
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The presence of C2C12-secreted adenosine significantly decreased the extravasation of cancer cells within the bone microenvironment.
“A deeper analysis revealed that the presence of C2C12‐secreted adenosine significantly decreased the extravasation of cancer cells within the bone microenvironment.”
From 3D Biomimetic Models to Reconstitute Tumor Microenvironment In Vitro: Spheroids, Organoids, and Tumor‐on‐a‐Chip (2023) · cites this paper as [132]
The Results sections on xenograft slice characterization and drug responses describe glioma tumor slices and drug testing, not cancer-cell extravasation in bone. Searches for C2C12, adenosine, and the claimed extravasation finding found no passage addressing it in our copy. (LLM, conf=0.77)
Experimental — accuracy not yet measuredIn a microvascular network embedded in a bone-like or muscle-like microenvironment, the extravasation rate and vessel permeability were much higher in the bone-mimicking microenvironment than in the muscle-mimicking microenvironment.
“It was found that the extravasation rate and vessel permeability were much higher in the bone‐mimicking microenvironment than in the muscle‐mimicking microenvironment.”
From 3D Biomimetic Models to Reconstitute Tumor Microenvironment In Vitro: Spheroids, Organoids, and Tumor‐on‐a‐Chip (2023) · cites this paper as [132]
The Results section on drug delivery describes diffusion into tumor slices, not extravasation from a microvascular network. The Discussion says the system does not reproduce in vivo delivery by capillaries. Searches for bone- and muscle-mimicking environments, extravasation, and vessel permeability found no comparison supporting the claim; page numbers were unavailable in our copy. (LLM, conf=0.75)
Experimental — accuracy not yet measuredMetastasis organ specificity and extravasation appear to be tightly coupled because specific chemo-attractant molecules are secreted by organ-specific stromal cells.
“Metastasis organ specificity and extravasation appear to be tightly coupled because specific chemo‐attractant molecules are secreted by organ‐specific stromal cells.”
From 3D Biomimetic Models to Reconstitute Tumor Microenvironment In Vitro: Spheroids, Organoids, and Tumor‐on‐a‐Chip (2023) · cites this paper as [132]
The Results describe drug testing on a colorectal cancer liver metastasis and identify stromal cells in tumor slices, but do not discuss how metastases select organs or extravasate. Searches for chemo-attractants and organ-specific stromal secretion found no passage addressing the proposed mechanism. (LLM, conf=0.76)
Experimental — accuracy not yet measured
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BackgroundSteinberg, E., Friedman, R., Goldstein, Y., Friedman, N., Beharier, O., Demma, J. A., Zamir, G. A., Hubert, A., & Benny, O. (2023) · Communications Biology · doi:10.1038/s42003-023-05531-5 · Cited by 57 · see citing works
“Many have tried to tackle this issue using two main approaches: extracting the biological sample 61 – 63 or dis-assembling the micro fl uidic device 64 – 67 .”
MethodMicrofluidic programmable strategies for channels and flow
Song, Y., Zhou, Y., Zhang, K., Fan, Z., Zhang, F., & Wei, M. (2024) · Lab on a Chip · doi:10.1039/d4lc00423j · Cited by 54 · see citing works
Microfluidic technologies for immunotherapy studies on solid tumours
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Emerging metabolomic tools to study cancer metastasis
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Microfluidics for interrogating live intact tissues
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“slices, or microdissected tissue, attractive in preclinical settings [19,29,30,51,52].”
BackgroundOrgan-on-Chip platforms to study tumor evolution and chemosensitivity
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Making In Vitro Tumor Models Whole Again
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ResultEngineering Heterogeneous Tumor Models for Biomedical Applications
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Microfluidic Surgery in Single Cells and Multicellular Systems
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Low-cost robotic manipulation of live microtissues for cancer drug testing
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Microtoxicology by microfluidic instrumentation: a review
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Design of a versatile microfluidic device for imaging precision-cut-tissue slices
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Establishing a Microfluidic Tumor Slice Culture Platform to Study Drug Response
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“Compared to traditional compound and tissue testing, micro fl uidic testing can incorporate various levels of complexity that more closely mimic in vivo physiology, leading to more accurate results (Shang et al., 2019; Horowitz et al., 2020).”
Drug investigation tool: Identifying the effect of drug on cell image by using improved correlation
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“Such trials strive to improve drug development’s speed and efficacy by offering a physiologically appropriate platform for human and animal trials .8,9 Measuring the drug effect by means of a correlation technique is important in the biological field.”
BackgroundPersonalized Drug Screening for Functional Tumor Profiling
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Bridging the Gap: How Organ‐on‐a‐Chip Technology Facilitates the Battle against Glioma
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Flat‐Field Lens Grating Microspectrometer for Spectroscopic Multiplex Bioassay
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Tumour-on-Chip Models for the Study of Ovarian Cancer: Current Challenges and Future Prospects
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“Multiplexed drug testing: Systems like the 40-channel platform by Horowitz et al. [52] allow high-throughput testing and could be adapted to OC samples.”
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Investigation of tumour environments through advancements in microtechnology and nanotechnology
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Self-citationAugmented 3D Printing for Multiscale Microphysiological Systems
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A prognostic matrix gene expression signature defines functional glioblastoma phenotypes and niches
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Tumor-on-chip platforms for transport phenotyping: decoding CAF-driven barriers to drug delivery
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Hyperthermia: Clinical Applications and Theoretical Models
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- Authors
- Horowitz, L. F., Rodriguez, A. D., Dereli-Korkut, Z., Lin, R., Castro, K., Mikheev, A. M., Monnat, R. J., Folch, A., & Rostomily, R. C.
- Affiliations
- University of Washington (US)
- Houston Methodist (US)
- Corresponding author
- Folch, A.
- Rostomily, R. C.
- ORCID
- Venue
- npj Precision Oncology
- Published
- 2020-05-19
- Volume
- 4
- Issue
- 1
- Pages
- 12-12
- ISSN
- 2397-768X (ISSN-L)
- PMC
- PMC7237421
- OpenAlex
- W3027676014
- Semantic Scholar
- bba2d103d02f84dffdb67932031c7d494dba47b4
- Cited by
- 88
- References
- 70
- Citations by year
- 2026: 12 · 2025: 12 · 2024: 14 · 2023: 16 · 2022: 17 · 2021: 9 · 2020: 8
- FWCI
- 3.93
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- npj Precision Oncology (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- University of Washington
- Consejo Nacional de Ciencia y Tecnología
- National Cancer Institute (P01CA077852, R01CA181445)
- National Institute of Neurological Disorders and Stroke (R21NS082542)
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › Microfluidic and Capillary Electrophoresis Applications
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Keywords
- microfluidic platform, drug susceptibility testing, glioma xenografts, personalized medicine, anticancer drug development, tissue microenvironment, digital manufacturing, precision oncology
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