The introduction of check-point immunotherapies such as pembrolizumab that target the Programmed Cell Death-Ligand interaction (PD-1/ PD-L1) that silence the immune response against cancer cells has provided a major breakthrough in several common cancers with poor survival rates (e.g., melanoma, lung cancer).

However, osteosarcoma patients appear fairly unresponsive to pembrolizumab. A key question is why?

Research carried out by Dr Olivier Pardo at Imperial College London suggests that a protein named FGF2 (basic fibroblast growth factor), and the signals that it triggers in osteosarcoma cells, may render osteosarcoma resistant to immunotherapy by inhibiting the activity of a major mediator of the immune response called interferon gamma.

What are the aims of this research project?

A research grant awarded to Dr Pardo aims to investigate how FGF2 decreases the ability of interferon gamma to act on osteosarcoma cells and how this reduces the activation of the immune system.

Importantly, drugs that inactivate FGF2 activity (e.g., AZD4547) exist and have been used in the clinic for other cancers.

A key aspect of this research is to determine if these drugs enable immunotherapy to be effective in osteosarcoma and then to test FGFR inhibitors/immune checkpoint inhibitors combinations in a preclinical model of osteosarcoma.

How could this project improve treatment options for osteosarcoma patients?

The introduction of immunotherapy has dramatically improved the outlook for patients with several types of cancer that previously had very low survival rates. However, this transformation has yet to occur for osteosarcoma.

This study aims to provide novel drug combinations that will enable immunotherapy to be efficient in osteosarcoma patients and deliver the same survival benefit that has been observed in other cancers.

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