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. Each patient responds differently to chemotherapy and we measure this by seeing how many cancer cells have been killed when the tumour is removed at surgery: if most cells have been killed, the patient is more likely to survive long -term. Also, some patients have troublesome side effects from the chemotherapy whereas others may not.

The effectiveness of chemotherapy depends on two things. Firstly, the amount of drug which is able to enter a cancer cell and secondly, how much is able to affect the target inside. Special transport systems operate at the surface of a cell, these may be more efficient in some people. 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 but not yet in osteosarcoma. This study therefore aims to investigate if there is a link between a patient's polymorphisms, their response to chemotherapy and severity of side effects in osteosarcoma.

Blood samples will be taken from 50 patients who have completed chemotherapy for osteosarcoma. These will be tested in a laboratory for the presence of all known polymorphisms which may affect the way the drug works. Regular blood, hearing, kidney and heart tests are performed during chemotherapy to monitor drug side effects and the results of these will be collected to discover if polymorphisms can influence these. 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 Rachel Windsor