How does interferon-alpha exert its antitumour activity in multiple myeloma?

The interferons (IFNs) have become accepted therapy in a range of hematological and non-hematological malignancies. One malignancy where IFN has demonstrated antitumour activity is multiple myeloma, where monotherapy with IFN-alpha yields a response rate of around 15%. It has also been suggested that myeloma patients may benefit from the addition of IFN-alpha in induction therapy and/or as maintenance treatment. The mechanism behind IFNs antitumour action in myeloma is, however, highly unclear. This probably means that current treatment regimens including IFN are far from optimal, since for example we do not know what factors that are responsible for resistance to IFN therapy in the individual patient, and furthermore we lack optimal tools to design new treatment strategies including IFN. The IFNs are capable of modulating a variety of cellular responses. One prominent effect being their cell growth inhibitory activity through induction of cell cycle arrest and apoptosis, which has also been suggested to be of major importance in IFNs antitumour action. In the present review possible antitumour mechanisms will be discussed, with the focus on ways that IFN may restrict myeloma cell growth.