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

Abstract

Abstract Introduction: 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. Materials and Methods: 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. Results: 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. Conclusions: 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.