Defining who benefits from treatment for melanoma


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Mark Middleton

University of Oxford, UK

Abstract

Defining who benefits from treatment for melanoma

The resistance of melanoma to treatment is well known. Despite 30 years of trials no drug, or combination of drugs, has improved upon single agent dacarbazine for the treatment of metastatic disease. Median survival remains resolutely stuck at 6 months. A wide variety of approaches to treatment has been tried, and it is interesting that responses are seen in 5-15% of patients irrespective of the putative mechanism of action of the agent(s) used.

The question therefore arises: is it always the same subset of patients who respond to treatment, or is benefit particular to the agent used? If the latter pertains then there will be a pressing need to identify the means of selecting patients for each treatment on offer. In the former case the clinical, pathological and genetic characteristics of responders and their tumours will also need to be elucidated, so as to select non-responders for experimental approaches and to delve further into the characteristics of ‘responding melanoma’. Defining what makes melanoma responsive to treatment might then yield potential targets for treatment.

Resolving these issues requires tissue, both from the patient and their tumour. Only by systematic collection of melanoma deposits and genetic characterisation of patients can we hope to gain sufficient data to answer this simplest of questions. The NCRI melanoma CSG intends to obtain ethical approval to allow the collection of archival materiel and blood from all responding patients whether treated within clinical trials or not. By comparing the characteristics of responders with those of the abundant treatment-resistant population we aim to identify those traits that are the hallmark of response, and gain an understanding of their ubiquity within responsive tumours.