Tumour necrosis factor alpha: a potential target for the therapy of solid tumours

Tumour necrosis factor alpha (TNFalpha), named for its antitumour properties, was isolated almost 30 years ago. It is a vital member of the multifunctional TNF superfamily and has important roles in immunity and cellular remodelling as well as influencing apoptosis and cell survival. Its central role in inflammation has led to the development of TNFalpha antagonists as effective therapies for rheumatoid arthritis and inflammatory bowel disease. In this review, we discuss the evidence which has accumulated during the past decade that implicates TNFalpha in inflammatory pathways that increase tumorigenesis. There is convincing evidence that under specific conditions TNFalpha is a tumour promoter and helps to produce the toxic effects associated with conventional cancer therapy, such as the cytokine release syndrome and cisplatin-induced nephrotoxicity. Several trials have been set up to investigate the role of TNFalpha antagonists in cancer. It is hoped that these agents inhibit the neoplastic process either alone or in combination with other agents, and ameliorate the side effects of cancer therapy.