Rapid screening of novel agents for combination therapy in sarcomas

14Citations
Citations of this article
18Readers
Mendeley users who have this article in their library.

This article is free to access.

Abstract

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. © 2013 Christopher L. Cubitt et al.

Cite

CITATION STYLE

APA

Cubitt, C. L., Menth, J., Dawson, J., Martinez, G. V., Foroutan, P., Morse, D. L., … Reed, D. R. (2013). Rapid screening of novel agents for combination therapy in sarcomas. Sarcoma, 2013. https://doi.org/10.1155/2013/365723

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free