Survival of individuals with osteosarcoma, the most common primary bone cancer which mainly affects teenagers and young adults, has not improved in the last 40 years since chemotherapy was introduced. The response to this toxic treatment is poor in nearly half of the treated patients, contributing significantly to their tumour returning, but the reasons for this failure have not been fully explained. Research into osteosarcoma has been significantly challenging due to the rarity of this disease and to the lack of good experimental systems to understand the causes of chemoresistance. Moreover, traditional drug testing using cancer cells in a dish has a poor track record of identifying new treatments, because they are too dissimilar from the tumours

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BACKGROUND TO THE RESEARCH PROJECT

Osteosarcoma, a form of bone cancer, becomes more challenging when it spreads, reducing the chance of survival. The Robert’s lab hypothesise that OS establishes itself in bones by interacting with osteoclasts, specialised cells responsible for breaking down bone tissue. Disrupting this interaction allows osteosarcoma to spread to the lungs.

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BACKGROUND TO THE RESEARCH PROJECT

Despite optimal management of localised osteosarcoma disease, over 50% of patients develop metastatic disease or recurrence, which lead to poor survival outcomes in approximately 19 months.  Immunotherapies, activating immune cells to attack cancers, became standard therapy in many other cancer types and enabled prolonged effects including prevention of recurrence and metastasis. However, osteosarcoma responds poorly to current standard immunotherapies due to A) inactivation of the immune system, B) resistance to immunotherapy, and C) difficulty in locally delivering drugs to tumour sites. Immunotherapies can achieve long-term effects including prevention of metastasis and recurrence. There remains huge room for improvement for immunotherapy in osteosarcoma as many patients suffer due to lack of treatment options and recurrence/metastasis.  

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BACKGROUND TO THE RESEARCH PROJECT

The project focuses on understanding and preventing the growth of cancer cells in osteosarcoma patients, as well as looking to stop the spread of cancer around the body. The ability of osteosarcoma to metastasise or spread to different sites is what makes it so aggressive and therefore focusing the research on this is really important. Michael is looking at repurposing a pre-existing drug, which is currently used to treat neonatal jaundice, to block the action of HO-1. HO-1 is a factor which is produced by osteosarcoma patients and prevents the activation of the immune system. By 'kick-starting' the immune system into action, the project will assess if the chemotherapy drugs are able to fight the cancer and stop it from moving to other areas of the body.

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