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

• Published in: PloS one Vol. 13; no. 9; p. e0203173
• Main Authors: Lohse, Ines, Al-Ali, Hassan, Volmar, Claude-Henry, D Alvarez Trotta, Annamil, Brothers, Shaun P, Capobianco, Anthony J, Wahlestedt, Claes
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 13.09.2018; Public Library of Science (PLoS)
• Subjects: Adenocarcinoma; Adenocarcinoma - drug therapy; Analysis; Antineoplastic Agents - therapeutic use; Behavioral sciences; Biology and Life Sciences; Biomarkers; Biotechnology; Cancer; Cancer therapies; Care and treatment; Cell Line, Tumor; Cell Survival - drug effects; Cisplatin; Clinical medicine; Diagnosis; Drug Evaluation, Preclinical; Drug Repositioning; Drug sensitivity testing; Drug testing; Epigenetic inheritance; Epigenetics; Esophageal cancer; Esophageal Neoplasms - drug therapy; Esophagus; FDA approval; Gemcitabine; Health risk assessment; Humans; Laboratories; Medical prognosis; Medical screening; Medicine; Medicine and Health Sciences; Mutation; Oncology; Patients; Psychiatry; Research and Analysis Methods; Sensitivity; Sequences; Surgery; Tomography; Toxicity; Treatment outcome; Tumor cell lines; Florida; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0203173

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. 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. 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. 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.