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Benchmarking of gastric cancer sensitivity to anti-cancer drugs ex vivo as a basis for drug selection in systemic and intraperitoneal therapy
BACKGROUND: The choice of drugs for treatment of advanced gastric cancer (GC) is empirical. The purpose of the current study was to benchmark ex vivo the sensitivity of GC tumor cells from patients to standard cytotoxic and some newly introduced targeted drugs (TDs), as a basis for drug selection in...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4304126/ https://www.ncbi.nlm.nih.gov/pubmed/25528067 http://dx.doi.org/10.1186/s13046-014-0110-9 |
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author | Hultman, Bo Mahteme, Haile Sundbom, Magnus Ljungman, Martin Larsson, Rolf Nygren, Peter |
author_facet | Hultman, Bo Mahteme, Haile Sundbom, Magnus Ljungman, Martin Larsson, Rolf Nygren, Peter |
author_sort | Hultman, Bo |
collection | PubMed |
description | BACKGROUND: The choice of drugs for treatment of advanced gastric cancer (GC) is empirical. The purpose of the current study was to benchmark ex vivo the sensitivity of GC tumor cells from patients to standard cytotoxic and some newly introduced targeted drugs (TDs), as a basis for drug selection in the treatment of GC. METHODS: Tumor cell samples from patients with GC were analyzed for sensitivity to 5-fluorouracil, cisplatin, oxaliplatin, irinotecan, mitomycin C, doxorubicin and docetaxel as well as for the targeted drugs bortezomib, sorafenib, sunitinib and rapamycin using a short-term in vitro assay based on retention of viable tumor cells of fluorescent fluorescein. Samples of normal mononuclear cells, chronic lymphocytic leukemia, ovarian cancer and colorectal cancer were included for comparison. RESULTS: The GC samples were essentially as sensitive to the standard drugs and the TDs as those from colorectal cancer whereas the ovarian cancer samples were more sensitive. The individual GC samples varied considerably in sensitivity to increasing concentrations of the clinically used standard drugs. In GC, cisplatin was cross-resistant to oxaliplatin and 5-fluorouracil which, on the other hand, was not cross-resistant to the other cytotoxic drugs. The activity of sunitinib did not obviously correlate to that of the standard drugs. CONCLUSION: Ex vivo assessment of drug sensitivity of tumor cells from patients with GC is feasible and may provide information that could be useful for selection of drugs for treatment. Drug sensitivity varies considerably between and within individual samples arguing for individualized selection of drugs for chemotherapy. |
format | Online Article Text |
id | pubmed-4304126 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-43041262015-01-24 Benchmarking of gastric cancer sensitivity to anti-cancer drugs ex vivo as a basis for drug selection in systemic and intraperitoneal therapy Hultman, Bo Mahteme, Haile Sundbom, Magnus Ljungman, Martin Larsson, Rolf Nygren, Peter J Exp Clin Cancer Res Research BACKGROUND: The choice of drugs for treatment of advanced gastric cancer (GC) is empirical. The purpose of the current study was to benchmark ex vivo the sensitivity of GC tumor cells from patients to standard cytotoxic and some newly introduced targeted drugs (TDs), as a basis for drug selection in the treatment of GC. METHODS: Tumor cell samples from patients with GC were analyzed for sensitivity to 5-fluorouracil, cisplatin, oxaliplatin, irinotecan, mitomycin C, doxorubicin and docetaxel as well as for the targeted drugs bortezomib, sorafenib, sunitinib and rapamycin using a short-term in vitro assay based on retention of viable tumor cells of fluorescent fluorescein. Samples of normal mononuclear cells, chronic lymphocytic leukemia, ovarian cancer and colorectal cancer were included for comparison. RESULTS: The GC samples were essentially as sensitive to the standard drugs and the TDs as those from colorectal cancer whereas the ovarian cancer samples were more sensitive. The individual GC samples varied considerably in sensitivity to increasing concentrations of the clinically used standard drugs. In GC, cisplatin was cross-resistant to oxaliplatin and 5-fluorouracil which, on the other hand, was not cross-resistant to the other cytotoxic drugs. The activity of sunitinib did not obviously correlate to that of the standard drugs. CONCLUSION: Ex vivo assessment of drug sensitivity of tumor cells from patients with GC is feasible and may provide information that could be useful for selection of drugs for treatment. Drug sensitivity varies considerably between and within individual samples arguing for individualized selection of drugs for chemotherapy. BioMed Central 2014-12-21 /pmc/articles/PMC4304126/ /pubmed/25528067 http://dx.doi.org/10.1186/s13046-014-0110-9 Text en © Hultman et al.; licensee BioMed Central. 2014 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Hultman, Bo Mahteme, Haile Sundbom, Magnus Ljungman, Martin Larsson, Rolf Nygren, Peter Benchmarking of gastric cancer sensitivity to anti-cancer drugs ex vivo as a basis for drug selection in systemic and intraperitoneal therapy |
title | Benchmarking of gastric cancer sensitivity to anti-cancer drugs ex vivo as a basis for drug selection in systemic and intraperitoneal therapy |
title_full | Benchmarking of gastric cancer sensitivity to anti-cancer drugs ex vivo as a basis for drug selection in systemic and intraperitoneal therapy |
title_fullStr | Benchmarking of gastric cancer sensitivity to anti-cancer drugs ex vivo as a basis for drug selection in systemic and intraperitoneal therapy |
title_full_unstemmed | Benchmarking of gastric cancer sensitivity to anti-cancer drugs ex vivo as a basis for drug selection in systemic and intraperitoneal therapy |
title_short | Benchmarking of gastric cancer sensitivity to anti-cancer drugs ex vivo as a basis for drug selection in systemic and intraperitoneal therapy |
title_sort | benchmarking of gastric cancer sensitivity to anti-cancer drugs ex vivo as a basis for drug selection in systemic and intraperitoneal therapy |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4304126/ https://www.ncbi.nlm.nih.gov/pubmed/25528067 http://dx.doi.org/10.1186/s13046-014-0110-9 |
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