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PLoS One. 2018 Sep 13;13(9):e0203173. doi: 10.1371/journal.pone.0203173. eCollection 2018.

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

Author information

1
Center for Therapeutic Innovation, Miller School of Medicine, University of Miami, Miami, Florida, United States of America.
2
Department of Psychiatry and Behavioral Sciences, Miller School of Medicine, University of Miami, Miami, Florida, United States of America.
3
Molecular Therapeutics Shared Resource, Sylvester Comprehensive Cancer Center, University of Miami, Miami, Florida, United States of America.
4
Sylvester Comprehensive Cancer Center, University of Miami, Miami, Florida, United States of America.
5
Miami Project to Cure Paralysis, Miller School of Medicine, University of Miami, Miami, Florida, United States of America.
6
Department of Neurological Surgery, Miller School of Medicine, University of Miami, Miami, Florida, United States of America.
7
Peggy and Harold Katz Drug Discovery Center, Department of Medicine, Miller School of Medicine, University of Miami, Miami, Florida, United States of America.
8
Molecular Oncology Program, DeWitt Daughtry Family Department of Surgery, Miller School of Medicine, University of Miami, Miami, Florida, United States of America.
9
Division of Surgical Oncology, DeWitt Daughtry Family Department of Surgery, Miller School of Medicine, University of Miami, Miami, Florida, United States of America.

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.

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