Multiplexed drug testing of tumor slices using a microfluidic platform

L F Horowitz,L F Horowitz,L F Horowitz,R C Rostomily,R C Rostomily,R C Rostomily,A Folch,A Folch,A D Rodriguez,A D Rodriguez,R J Monnat,R J Monnat,Z Dereli-Korkut,Z Dereli-Korkut,K Castro,K Castro,A M Mikheev,A M Mikheev,R Lin,R Lin

doi:10.1038/s41698-020-0117-y

L F Horowitz, L F Horowitz + Show 18 more

Open Access

https://doi.org/10.1038/s41698-020-0117-y

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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.

Highlights

Despite advances in targeted and immune therapies, cancer treatment continues to face enormous challenges as it moves toward the goal of rationally chosen, personalized therapy[1,2].Critically, molecular features alone can guide treatment, they cannot reliably predict an individual patient’s functional response to targeted, immune, or conventional treatment
The microfluidic device is digitally manufactured by laser-cutting in poly(methyl methacrylate) (PMMA), as we have recently described in detail[47]
To select candidate drugs for testing on slices, we performed microfluidic device can deliver drugs applied two lanes apart high-throughput drug screens in 2D cell culture with the GBM U87 without significant cross-contamination in the tissue directly and GBM8 glioma stem cell lines used to generate the xenograft above the delivery lanes, we examined the lateral diffusion of tumors in this study

Summary

Introduction

Molecular features alone can guide treatment, they cannot reliably predict an individual patient’s functional response to targeted, immune, or conventional treatment. In vitro functional tests on an individual’s cancer could help to predict that patient’s outcome, even without any molecular knowledge. Despite success in identifying drugs or small molecules that target specific mutations and pathways[3] the majority of cancer patients do not currently qualify for genomically targeted drug treatment and responses are limited by cell intrinsic resistance and microenvironmental factors[2]. It has become clear that the presence of a targetable or “actionable” mutation does not guarantee the success of drug treatment[2], and may lead to substantially different outcomes for different patients and for different cancers[4]

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