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

Ines Lohse, Hassan Al-Ali, Claude Henry Volmar, Annamil D. Alvarez Trotta, Shaun P Brothers, Anthony J Capobianco, Claes R Wahlestedt

Research output: Contribution to journalArticle

Abstract

Background Esophageal cancer remains one of the hardest cancers to treat with rising incidence rates, low overall survival and high levels of treatment resistance. The lack of clinically available biomarkers hinder diagnosis and treatment stratification. While large scale sequencing approaches have uncovered a number of molecular makers, little has translated in the routine treatment of esophageal cancer patients. Material and methods We evaluate the treatment response towards a panel of 215 FDA-approved and 163 epigenetic compounds of 4 established and 2 patient-derived esophageal cancer cell lines. Cell viability was evaluated after 72h of treatment using cell titer glow. The drug sensitivity testing results for gemcitabine and cisplatin were validated using clonogenic assays. Results The tested cell lines display different drug sensitivity profiles, although we found compounds that display efficacy in all of the tested established or patient-derived cell lines. Clonogenic assays confirmed the validity of the drug sensitivity testing results. Using the epigenetic library, we observed high sensitivity towards a number of epigenetic modifiers. Discussion Ex vivo drug sensitivity testing may present a viable option for the treatment stratification of esophageal cancer patients and holds the potential to greatly improve patient outcome while reducing treatment toxicity.

Original languageEnglish (US)
Article numbere0203173
JournalPLoS One
Volume13
Issue number9
DOIs
StatePublished - Sep 1 2018

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Drug Repositioning
esophageal neoplasms
adenocarcinoma
Adenocarcinoma
Cells
drugs
Esophageal Neoplasms
epigenetics
Testing
gemcitabine
Pharmaceutical Preparations
cell lines
Assays
Epigenomics
testing
Cell Line
Biomarkers
Therapeutics
cisplatin
modifiers (genes)

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Ex vivo drug sensitivity testing as a means for drug repurposing in esophageal adenocarcinoma. / Lohse, Ines; Al-Ali, Hassan; Volmar, Claude Henry; Alvarez Trotta, Annamil D.; Brothers, Shaun P; Capobianco, Anthony J; Wahlestedt, Claes R.

In: PLoS One, Vol. 13, No. 9, e0203173, 01.09.2018.

Research output: Contribution to journalArticle

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