Osteosarcoma is the most common primary tumour of the bone, and the second leading cause of cancer-related death in children and young adults. Although this sarcoma is relatively rare, osteosarcoma in adults remains a devastating diagnosis for both a patient and their family.
Aggressive surgery with chemotherapy does increase survival when the cancer is in its early stages, however, these treatments often result in lifelong health problems. The outlook for more advanced osteosarcoma is poor, with less than 20% of people surviving for 5 years after diagnosis. The fact this rate has not improved in 30 years highlights the need for new and improved therapies.
Professor Watkins and his team have shown that a specific molecular pathway, called the Hedgehog pathway, is involved in osteosarcoma. In fact, osteosarcomas are dependent on this pathway to grow. Drugs that block the Hedgehog pathway could potentially treat osteosarcomas by stopping the growth of the tumour. However, no genetic mutations in this pathway have been found yet, and this means there is no way of identifying which patients could benefit from this type of treatment.
Over the last year, Professor Watkins has found two mutations that are common in osteosarcomas. When both of these mutations are present in the same tumour, it becomes dependent on the Hedgehog pathway to grow. This means these osteosarcomas would respond to drugs that block this pathway.
Professor Watkins has uncovered a method to predict which osteosarcomas can be treated with Hedgehog pathways blockers. Mutations in both of these genes occurs in around 40% of all osteosarcomas, which means this discovery could have a significant impact on a large proportion of patients.
By understanding the Hedgehog pathway and its relationship to osteosarcoma, Professor Watkins and his team are laying the foundation for a clinical trial on this therapy. They are also developing the methods and tools needed to successfully translate these Hedgehog-based treatments into clinical practice.