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Microphysiological Drug-Testing Platform for Identifying Responses to Prodrug Treatment in Primary Leukemia.

Furkan Gökçe1, Alicia Kaestli1, Christian Lohasz1

  • 1Department of Biosystems Science and Engineering, ETH Zurich, Basel, BS, 4058, Switzerland.

Advanced Healthcare Materials
|January 18, 2023
PubMed
Summary

A new microfluidic platform enables testing of prodrugs, like ifosfamide, in pediatric leukemia. This approach accurately predicts patient-specific drug responses, advancing precision chemotherapy for difficult leukemia subtypes.

Keywords:
acute lymphoblastic leukemiadrug response profilingmicrophysiological systemspersonalized healthprodrugs

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Area of Science:

  • Oncology
  • Pharmacology
  • Biomedical Engineering

Background:

  • Pediatric leukemia survival rates are improving, but some subtypes remain challenging.
  • Current drug screening platforms struggle to assess prodrugs, which require metabolic activation.
  • Tailoring treatments with drug sensitivity testing is crucial for high-risk pediatric leukemia patients.

Purpose of the Study:

  • To develop a microphysiological platform for evaluating prodrug efficacy in pediatric leukemia.
  • To overcome limitations of traditional assays in testing prodrugs and their metabolites.
  • To enable personalized chemotherapy selection through patient-specific drug response testing.

Main Methods:

  • Development of a microfluidic platform for co-culturing leukemia cells, bone marrow stromal cells, and liver microtissues.
  • Controlled physical interactions between diverse cell types within the microfluidic system.
  • Recapitulation of hepatic prodrug activation, specifically for ifosfamide, in a physiologically relevant model.

Main Results:

  • The platform successfully recapitulated hepatic prodrug activation of ifosfamide.
  • Patient-derived leukemia samples showed varying sensitivities to the prodrug ifosfamide.
  • The microfluidic system accurately tested prodrugs, including unstable metabolites, under relevant conditions.

Conclusions:

  • The developed microfluidic platform accurately assesses prodrug efficacy and patient-specific sensitivities.
  • This technology facilitates the testing of prodrugs, including short-lived metabolites.
  • The platform shows significant potential for clinical translation in precision chemotherapy selection for pediatric leukemia.