Dr Randall on the Use of Osteosarcoma Spheroid Models to Streamline Preclinical Therapeutic Development

[Spheroids] are easy to produce [and] potentially introduce agents that we are considering for clinical development. If we get an effect, we can take it to the engineered bone marrow model, then into a clinical trial.”

R. Lor Randall, MD, FASCO, chair of the Department of Orthopedic Surgery and the David Linn Endowed Chair for Orthopedic Surgery at the University of California, Davis, discussed the development and application of three-dimensional (3D) spheroid models for high-throughput drug screening in osteosarcoma research.

Randall and colleagues have generated spheroids using various osteosarcoma cell lines, including highly metastatic and less aggressive lines, to evaluate therapeutic response in a more physiologically relevant system than traditional two-dimensional cultures. The spheroids—composed of compact spheres of sarcoma cells—incorporate basic mechanical and microenvironmental properties that more closely resemble in vivo tumors, he explained. This 3D structure enables a more accurate assessment of agent activity prior to advancing compounds into complex validation models or clinical trials, Randall noted.

Although spheroids do not replicate the full complexity of engineered bone marrow constructs, their simplicity and ease of production make them an effective platform for initial screening, he continued. Randall emphasized that agents showing activity in the spheroid model can then be advanced to the more intricate engineered bone marrow system for further evaluation. This stepwise approach allows researchers to reserve more resource-intensive testing for compounds with demonstrated preliminary efficacy in spheroids.

Randall further explained that developing this efficient screening model is critical to accelerating therapeutic discovery in osteosarcoma, a historically challenging disease with limited treatment advances. By streamlining candidate evaluation through high-throughput spheroid systems before proceeding to complex models and clinical investigation, researchers can improve the prioritization of promising therapies for patients with osteosarcoma, he concluded.