Biomarkers for Osteosarcoma Response to Chemo

Clinical advances in the treatment of osteosarcoma are rare, and as I have highlighted in the past (here, for example), there are no signs of improvements in outcomes in recent years. The standard treatment for osteosarcoma is neo-adjuvant chemotherapy (using multiple chemo drugs) to shrink the tumours and then surgery to remove them. One of the things that we do know about osteosarcoma is that good response to chemotherapy (defined as greater than 90% tumour cell death), is associated improved chances overall survival. In other words the more the tumour is killed by the chemo the more chance there is that the surgery removes it all and that there is a lower risk that it will have metastasised. However, assessing the rate of tumour kill is hard to do - at the moment you actually need to remove a sample of the tumour to analyse it. Unlike some other forms of cancer, there are no generally recognised bio-markers that you can use as a way of assessing the success rate during the chemotherapy treatment protocol. Nor is there any way of establishing which patients will respond well to chemotherapy and those that won't.

A just published study has looked at the relationship between the expression of the p16 gene in osteosarcoma and response to chemotherapy. The results were clear - loss of p16 expression in tumours is strongly correlated with a worse response to chemotherapy. This backs up previous work which looked at the relationship between p16 and survival in osteosarcoma. This new study now provides the link to explain this relationship. Lower p16 expression causes less sensitivity to chemotherapy, leading to less tumour cell necrosis and ultimately leading to worse outcomes.

This means that p16 expression can be checked at initial diagnosis and treatment options adjusted accordingly. For patients with high levels of p16 expression then the standard treatments will have more chance of success. For those with little or no p16 expression, other options will need to be considered.

Details of this new study are here: http://www.ncbi.nlm.nih.gov/pubmed/22578565