Exploring a novel drug treatment for osteosarcoma

Osteosarcoma is a devastating malignancy that affects children and young adults. Despite advances in combined adjuvant chemotherapy and limb-sparing surgery, the 5-year survival has reached a plateau of 60-70%, dropping significantly to ~20% with lung metastatic disease.

Novel approaches are therefore stillrequired to identify and block the signals that drive the cancer cells to grow and metastasise to the lungs. One of the current breakthroughs in the cancer field is understanding how the immune system can be boosted to fight against the cancer. Indeed, standard chemotherapy treatment suppresses the immune system, allowing the cancer to escape attack from immune cells.

There are special cells called tumour-associated macrophages (TAMs) that are hijacked by the cancer cells and make factors that evade attack of cancer cells by the immune system. One treatment strategy is therefore to target TAMs to “kick-start” thebody’s own defence system. We have established in our laboratory the first pre-clinical mouse model of osteosarcoma that mimics many features of human disease. We have shown that TAMs are present in these bone tumours, although their function is unknown, but our preliminary observations have shown that they express this enzymecalled Heme Oxygenase-1 (HO-1) which can modulate the immune response.

This allows us to predict thatblocking HO-1 would provide a potential therapy for osteosarcoma and metastasis by reactivating the immune system. Fortunately, there is a FDA-approved drug that inhibits HO-1, called SnMP, that is already used in patients for neonatal jaundice. This is very exciting, as the concept of “drug repurposing”, ie. the use of existing, approved drugs for new therapeutic purposes, is now a major therapeutic strategy in translational medical research. Thus, in this project we will provide evidence that SnMP inhibits tumour formation in pre-clinical osteosarcoma models, that will pave the way for future patient treatment.