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.