Identifying predictive biomarkers for the therapeutic efficacy of check point inhibitors

Summary

In excess of 200,000 cases of malignant melanoma cases are diagnosed every year worldwide. In fact, malignant melanoma is the fifth most common cancer in the UK, accounting for 4% of all new cases in the UK every year (CRUK Statistics, 2013). In addition, many malignant melanomas progress to become metastatic. Thus, there is an urgent need to develop effective strategies to treat metastatic melanoma patients. Monoclonal antibodies (e.g. nivolumab and pembrolizumab), capable of blocking the programmed death-1 receptor/programmed death ligand-1 (PD-1/PD-L1) pathway (PD pathway), have recently been approved by the U.S. Food and Drug Administration (FDA, 2014) for the treatment of metastatic melanoma patients. Anti-PD pathway therapy has yielded impressive clinical benefits such as tumour regression and improved survival, by restoring T-cell mediated immunity. However, despite the great excitement about the use of these "checkpoint inhibitors", a proportion of patients do not respond (40-60%) and in addition, some can develop autoimmune symptoms. It is therefore important that we identify biomarkers that can more accurately predict which patients would benefit from these expensive drugs and pinpoint those that are more likely to suffer the auto-immune side effects. Here, we are requesting funds to conduct a comprehensive analysis of PDL-1, PD-1 and co-inhibitory receptor expression in melanoma patients treated with monoclonal antibodies that block the PD pathway as a step towards identifying biomarkers that can be used to predict response to treatment.