In 2016, we awarded an Idea Grant to Dr Helen Knowles (University of Oxford) to investigate the potential of targeting a protein called angiopoietin-like 4 (ANGPTL4) to reduce the metastatic spread of osteosarcoma, with the long-term objective of improving the survival for patients with aggressive disease.
The results from the Oxford group indicated that ANGPTL4 is involved in many aspects of the metastatic spread of osteosarcoma, including rapid tumour growth, bone digestion and migration. This exciting finding makes ANGPTL4 a target for a new therapy that could potentially block or slow down osteosarcoma progression and prevent metastasis.
Helen’s exciting results initiated a collaboration with Professor Nguan Soon Tan (Nanyang Technological University, Singapore), Professor Dominique Heymann (University of Sheffield and University of Nantes, France) and Professor Adrienne Flanagan (University College London), to study how treatment with an ANGPTL4 blocking protein could affect osteosarcoma disease progression in a laboratory model of disease. The results showed a dramatic reduction in lung metastasis formation as well as a reduction in the formation of bone outside the skeleton, a characteristic of osteosarcoma that causes great pain and disability.
Unfortunately, Covid-19 related issues stopped the work. In 2022, a newly funded Idea Grant allowed Dr Knowles to continue this exciting research and answer two key questions:
- Does this treatment also reduce growth of the primary tumour within the bone?
- Does the amount of ANGPTL4 protein present in human osteosarcoma tissues relate to the clinical characteristics of the tumour?
What were the results of this research project?
Treatment with an ANGPTL4-blocking protein reduced lung metastases and that the formation of extra bone outside the normal skeleton (a characteristic of osteosarcoma that causes great pain and disability) was almost completely prevented.
Future work in this ongoing project will try and understand how the beneficial effects of anti-ANGPTL4 treatment might occur, as well as investigating whether greater effects to inhibit tumour growth can be achieved by combining the treatment with other standard therapies.
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