Ex vivo drug sensitivity testing as a means for drug repurposing in esophageal adenocarcinoma

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Drug Repurposing Hypothesis Generation Using the "RE:fine Drugs" System

Published on: December 11, 2016

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Ines Lohse1,2,3, Hassan Al-Ali4,5,6,7, Claude-Henry Volmar1,2,3

  • 1Center for Therapeutic Innovation, Miller School of Medicine, University of Miami, Miami, Florida, United States of America.

Plos One
|September 14, 2018
PubMed
Abstract

Insights

Esophageal cancer drug sensitivity testing shows promise for personalized treatment. Ex vivo testing of epigenetic compounds may improve patient outcomes and reduce toxicity in esophageal cancer care.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Esophageal cancer presents significant treatment challenges due to rising incidence, low survival rates, and treatment resistance.
  • Lack of effective biomarkers impedes diagnosis and treatment stratification for esophageal cancer patients.
  • Limited translation of molecular discoveries into routine clinical practice for esophageal cancer management.

Purpose of the Study:

  • To evaluate the drug sensitivity of esophageal cancer cell lines against FDA-approved and epigenetic compounds.
  • To identify potential therapeutic agents for esophageal cancer treatment stratification.
  • To assess the utility of ex vivo drug sensitivity testing for improving patient outcomes.

Main Methods:

  • Treatment response evaluation of 4 established and 2 patient-derived esophageal cancer cell lines.
  • Screening of 215 FDA-approved and 163 epigenetic compounds.
  • Cell viability assays (CellTiter-Glo) and validation with clonogenic assays for gemcitabine and cisplatin.

Main Results:

  • Esophageal cancer cell lines exhibited varied drug sensitivity profiles.
  • Specific compounds demonstrated efficacy across all tested cell lines.
  • High sensitivity was observed for several epigenetic modifiers, validated by clonogenic assays.

Conclusions:

  • Ex vivo drug sensitivity testing offers a viable strategy for esophageal cancer treatment stratification.
  • This approach has the potential to significantly enhance patient outcomes.
  • Personalized drug sensitivity testing may reduce treatment-related toxicity in esophageal cancer patients.

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