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 language | English (US) |
|---|---|
| Article number | e0203173 |
| Journal | PLoS One |
| Volume | 13 |
| Issue number | 9 |
| DOIs | |
| State | Published - Sep 1 2018 |
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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 journal › Article
}
TY - JOUR
T1 - Ex vivo drug sensitivity testing as a means for drug repurposing in esophageal adenocarcinoma
AU - Lohse, Ines
AU - Al-Ali, Hassan
AU - Volmar, Claude Henry
AU - Alvarez Trotta, Annamil D.
AU - Brothers, Shaun P
AU - Capobianco, Anthony J
AU - Wahlestedt, Claes R
PY - 2018/9/1
Y1 - 2018/9/1
N2 - 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.
AB - 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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UR - http://www.scopus.com/inward/citedby.url?scp=85053250886&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0203173
DO - 10.1371/journal.pone.0203173
M3 - Article
C2 - 30212533
AN - SCOPUS:85053250886
VL - 13
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 9
M1 - e0203173
ER -