Study: A Drug Combination that Inhibits the Growth of Pediatric Ewing Sarcoma

The combination of two different drugs, focal adhesion kinase (FAK) and Aurora kinase B, can inhibit the growth of pediatric Ewing sarcoma, according to the findings of a study published in Clinical Cancer Research.

Ewing sarcoma is an aggressive form of bone cancer that develops in childhood. Although modern treatments can cure Ewing n approximately 70% of patients with a localized form of the disease, these therapies are ineffective in patients with metastases or relapse.

To conduct this study, researchers identified possible treatment combinations for Ewing sarcoma by performing a small-molecule library screen to pinpoint all compounds that work synergistically with FAK inhibitors in impeding Ewing cell progression. The researchers validated the activity level of top-scoring class of compounds across several Ewing cell lines in both in vitro and xenograft models, respectively, of Ewing sarcoma.

Successful Synergy

Upon analysis of the screening, researchers found that multiple Aurora kinase inhibitors scored as synergistic with FAK inhibition in this screen. According to the study results, when combined with FAK inhibitors, Aurora kinase B inhibitors were more synergistic across a larger range of concentrations. The study found that a combination of AZD-1152, an Aurora kinase B inhibitor, along with PF-562281 or VS-4718, both FAK-selective inhibitors, resulted in Ewing sarcoma cell inhibition at concentrations that were shown to minimally change when either drug was used independently. Moreover, the results found that the specific the combination notably hindered tumor growth in multiple xenograft models.

In their conclusion, the authors wrote that this “study provides preclinical support for the consideration of a clinical trial testing the safety and efficacy of this combination for patients with Ewing sarcoma.”

The study’s corresponding author, Brian Crompton, MD, said in a press release that “these studies are beginning to pave the way for the development of new and more effective treatments for patients with Ewing sarcoma that are expected to have less toxicity than the current standard treatment for this disease.”

Source: Clinical Cancer Research, EurekAlert