Osteosarcoma is the commonest bone cancer in children and young people. The best known treatment is a combination of three chemotherapy drugs called methotrexate, doxorubicin and cisplatin. However, just under half the patients do not respond well to this treatment. Their survival 5 years after their illness is 50% compared to 75% in patients who respond well. Additionally, some patients experience long term side effects from their chemotherapy.

It is not clear why some patients respond poorly or have serious side effects. The effectiveness of chemotherapy depends on two things. Firstly, how much of the drug is able to enter a cancer cell and secondly, how much is able to affect the target inside. Targets may be the cell machinery or special proteins called enzymes. Different forms of some enzymes, called polymorphisms, are found in different people. These can affect the way a person responds to a particular drug.

Some research has already shown that different enzyme types can affect survival in some cancers. This work has not yet been done in osteosarcoma. This study will investigate if there is any link between the polymorphisms a patient has and their response to chemotherapy in osteosarcoma. We would also like to see if the polymorphisms influence long-term side effects from chemotherapy. Blood samples will be taken from patients who are going through treatment or who have already finished. The presence of several different polymorphisms will be tested for in a laboratory. During chemotherapy for osteosarcoma, all patients have hearing, blood and heart tests to monitor drug side effects.

The results of these will be collected to provide information about the seriousness of side effects. We may then discover if polymorphisms can influence this too. The long term goal of this project is to discover if genetic "make-up" can change the way osteosarcoma responds to treatment. Ultimately, we would wish to use this knowledge to further understand tumour resistance and improve survival.

Dr Rachael Windsor, University College Hospital, London