Dr Walker-Mimms on Outcomes With Filanesib in Ewing and Clear Cell Sarcoma

Hannah Walker-Mimms, MS, Cancer Biology PhD candidate, research associate, Moffitt Cancer Center, discusses outcomes from an FDA-approved library screen which revealed that Ewing and clear cell sarcomas have increased sensitivity to filanesib (ARRY-520) over other cancer types.

When conducting this research, Walker-Mimms and colleagues had access to extensive resources, including multiple libraries and a liquid handler that streamlines larger drug screens, enhancing efficiency in identifying treatments beneficial to patients. In a specific drug-screening study, investigators focused on a clear cell sarcoma cell line alongside a melanoma cell line due to historical misclassification of clear cell sarcoma as melanoma, she reports, explaining that the goal of this study was to identify compounds that are selectively effective against clear cell sarcoma compared with melanoma as a control.

Following a viability assay after 72 hours, investigators identified the top 10 compounds that selectively targeted clear cell sarcoma without affecting melanoma cells, she explains. Notably, 1 of these compounds, known as KIF11, emerged as a significant hit target in the screen, according to Walker-Mimms. Subsequently, investigators assessed whether KIF11 could serve as an effective therapy for both clear cell sarcoma and Ewing sarcoma, Walker-Mimms states. The findings demonstrated efficacy of the drug in both sarcomas, contrasting with the drug’s activity in melanoma, she emphasizes.

Further investigation revealed an intriguing relationship between fusion proteins and KIF11, indicating an upregulated pathway contributing to the drug’s efficacy, Walker-Mimms expands, adding that literature supports these findings when describing the main mechanism of action of filanesib. Furthermore, resources allowed investigators access to detailed imaging of cells during mitotic stages, showing that cells treated with filanesib predominantly arrest in prophase and untreated cells progress through mitosis, exhibiting disrupted mitotic spindles, Walker-Mimms says.

Investigators observed significant differences in tumor growth and survival in mouse models for clear cell sarcoma and Ewing sarcoma that were treated with filanesib, she explains. These data underscore the translational effectiveness of findings from the in vitro studies to in vivo models, Walker-Mimms notes. Moving forward, investigators aim to conduct additional preclinical studies to further evaluate the potential of filanesib, Walker-Mimms concludes.