Efficacy of Pazopanib on Primary Patient-derived Undifferentiated Malignant Round Cell Sarcoma Line

Undifferentiated round cell tumours (URCTs) are rare and less researched Ewing-like mesenchymal tumours that primarily affect bones and soft tissues. Therapeutic options for advanced URCT are limited. Pazopanib, a multi-tyrosine kinase and angiogenesis inhibitor, is currently used for managing advanced soft-tissue sarcoma. However, its efficacy in the treatment of URCT remains uncertain and has not been established. In this study, we have cultured and characterised a patient-derived URCT cell line to understand the in vitro growth properties and anti-cancer agent sensitivity. Primary cell culture was performed by mechanical and enzymatic dissociation of URCT tissue specimens to derive a cell line. Morphology, growth properties and immunological features characterised the cells. Further, the in vitro sensitivity for clinically used anti-cancer drugs was evaluated. The URCT cell line was established from a high-grade round-cell tumour patient. The cells had mesenchymal morphology and showed cyclin B3 (CCNB3) positivity, which was confirmed in the tissue from the patient. The cells exhibited an anchorage-independent growth property and aggregated to form spheroids in a non-adherent in vitro system. Anti-cancer agents vincristine, doxorubicin, etoposide and pazopanib inhibited URCT cell proliferation. Pazopanib exhibited cytotoxic action in URCT cells, leading to cell death. This is an early report of cultured URCT cells expressing CCNB3, studied in vitro. The patient-derived model suggests the efficacy of pazopanib in URCT cells. The characterised line will be helpful to advance sarcoma studies.