Biological response modifiers in the treatment of malignant brain tumours: Role of interferons and retinoids

The retinoids and type I interferons constitute the 2 principal classes of biological response modifiers (BRMs) that have demonstrated activity in the treatment of malignant cerebral tumours, and are associated with fewer of the adverse effects induced by conventional chemotherapeutic agents. These BRMs share numerous common characteristics that may underlie their observed clinical efficacy. First, both classes of agent activate intracellular signal transduction pathways that, at numerous points, are capable of antagonising the oncogenic effects of growth factor-stimulated pathways in tumour cells. Secondly, the intracellular signals initiated by these BRMs ultimately lead to the activation of a multitude of genes; these genes, in turn, encode anti- tumourigenic functions that are distinct from the classic cytotoxic effects of conventional chemotherapeutic agents, such as the induction of differentiation and the inhibition of angiogenesis. Thirdly, while both classes of BRMs have demonstrated encouraging results in clinical trials when used as monotherapy, there is evidence that they may act synergistically when used in combination with each other or with conventional chemotherapeutic agents. With further refinements, the BRMs may develop into important adjunctive agents in the treatment of patients with malignant brain tumours.