A new, less toxic way to treat malignant melanoma (skin cancer) is being developed by medicinal chemists at Reading University. They have produced a range of prodrugs: compounds that offer the potential to be converted to toxic molecules only within the vicinity of tumours. These prodrugs aim to reduce the toxicity of treatment.
Malignant melanoma is a highly aggressive skin cancer. If caught early, it can be treated surgically, but in many cases the disease has spread by the time it is diagnosed and chemotherapy is needed.
The problem with current cancer chemotherapy drugs is their tendency to be toxic to healthy cells in the body, producing severe side effects. The new drug treatment under development specifically targets the tumour. It does this by taking advantage of an enzyme (tyrosinase) that is generally present at increased levels in melanoma cells compared with normal melanocytes, and is virtually absent from other cells.
Dr Helen Osborn, from the University’s School of Pharmacy, explained:
“Tyrosinase is not in itself a problem. But its presence in melanoma provides us with a tool that we can use to convert a non-toxic prodrug into a toxic agent.”
Dr Osborn says that, as well as reducing toxicity, the prodrug approach has the advantage of delivering high concentrations of drug to the tumour, which should discourage development of resistant tumours.
“Often, only a small amount of drug reaches the tumour and any surviving cells can develop resistance,” she says.
Dr Osborn says that no compound is yet ready for clinical testing, as further work is needed to improve the prodrug selectivity for melanoma cells. “We want it to be very toxic in tyrosinase-containing cells and completely non-toxic in cells that do not contain tyrosinase,” she explains.