INTERFERON AND RETINOIC ACID IN HUMAN CAN CER - CLINICAL AND MECHANISTIC STUDIES

Retinoic acid (RA) and interferons (IFN) are negative regulators of ce ll proliferation. A number of clinical trials were thus carried out in cancer therapy with RA and/or IFN. In vitro and in vivo, their combin ation leads to a more potent cell growth inhibition. Moreover, RA and IFN act cooperatively to increase the expression of many IFN-stimulate d genes, leading also to a higher cell differentiation and inhibition of viral replication. However, the molecular mechanisms by which RA an d IFN potentiate each other are not fully understood. The cooperative effects by RA and IFN are mediated through multiple pathways. RA cause s the induction and secretion of TFN alpha. RA also stimulates the IFN regulatory factor gene expression (IRF1 and p48). Additional mechanis ms could be involved as RA increases the level of signal transducing a ctivators of transcription (Stat) proteins, and thus enhances the IFN- induced Stat activation.