Cylinromatosis and aspirin

Cylindromatosis is a rare form of skin cancer. Understanding its basic molecular pathway has pointed to the possible use of aspirin in its treatment. Cylindromatosis arises from the hair follicles, sweat glands and sebaceous glands. The tumours, which lie in the dermis, are inherited as an autosomal dominant predisposition, and give rise to multiple disfiguration. Current treatment involves surgical removal and skin grafting.

Professor Ashworth's laboratory became involved in the characterisation of the mutated gene (CYLD) that makes patients susceptible to the disease. The team identified germline mutations in CYLD in most of the patients. The gene encodes a protein of 956 aminoacids with no extensive sequence similarity to other known proteins.

Loss of normal CYLD activity leads to loss of apoptosis through several complex pathways. aspirin at high doses counteracts these effects of loss of CYLD, so cells from patients with cylindromatosis that are treated with aspirin may go on to commit suicide rather than survive and grow. The systemic dose for aspirin to do so, however, is too high for it to be given by mouth in humans. A trial has started in Holland using topical aspirin on the tumours and Professor John Burn is currently treating one patient in the UK with topical application of an NSAID. Meanwhile other NSAIDs are being tested for their effect on cylindromatosis cancer cells.

Professor Angus Dalgleish, Professor of Oncology, at St. George's Hospital Medical School, London, followed Dr Farmer with a talk on bladder and prostate cancer.