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Rapid Screening of Novel Agents for Combination Therapy in Sarcomas
Joint Authors
Sullivan, Daniel M.
Bui, Marilyn M.
Martinez, Gary V.
Menth, Jiliana
Dawson, Jana
Reed, Damon R.
Cubitt, Christopher L.
Letson, G. Douglas
Foroutan, Parastou
Morse, David L.
Source
Issue
Vol. 2013, Issue 2013 (31 Dec. 2013), pp.1-12, 12 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2013-10-24
Country of Publication
Egypt
No. of Pages
12
Main Subjects
Abstract EN
For patients with sarcoma, metastatic disease remains very difficult to cure, and outcomes remain less than optimal.
Treatment options have not largely changed, although some promising gains have been made with single agents in specific subtypes with the use of targeted agents.
Here, we developed a system to investigate synergy of combinations of targeted and cytotoxic agents in a panel of sarcoma cell lines.
Agents were investigated alone and in combination with varying dose ratios.
Dose-response curves were analyzed for synergy using methods derived from Chou and Talalay (1984).
A promising combination, dasatinib and triciribine, was explored in a murine model using the A673 cell line, and tumors were evaluated by MRI and histology for therapy effect.
We found that histone deacetylase inhibitors were synergistic with etoposide, dasatinib, and Akt inhibitors across cell lines.
Sorafenib and topotecan demonstrated a mixed response.
Our systematic drug screening method allowed us to screen a large number of combinations of sarcoma agents.
This method can be easily modified to accommodate other cell line models, and confirmatory assays, such as animal experiments, can provide excellent preclinical data to inform clinical trials for these rare malignancies.
American Psychological Association (APA)
Cubitt, Christopher L.& Menth, Jiliana& Dawson, Jana& Martinez, Gary V.& Foroutan, Parastou& Morse, David L.…[et al.]. 2013. Rapid Screening of Novel Agents for Combination Therapy in Sarcomas. Complexity،Vol. 2013, no. 2013, pp.1-12.
https://search.emarefa.net/detail/BIM-1011448
Modern Language Association (MLA)
Cubitt, Christopher L.…[et al.]. Rapid Screening of Novel Agents for Combination Therapy in Sarcomas. Complexity No. 2013 (2013), pp.1-12.
https://search.emarefa.net/detail/BIM-1011448
American Medical Association (AMA)
Cubitt, Christopher L.& Menth, Jiliana& Dawson, Jana& Martinez, Gary V.& Foroutan, Parastou& Morse, David L.…[et al.]. Rapid Screening of Novel Agents for Combination Therapy in Sarcomas. Complexity. 2013. Vol. 2013, no. 2013, pp.1-12.
https://search.emarefa.net/detail/BIM-1011448
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1011448