A major challenge in cancer research is to discover drugs with high selectivity and minor side-effects. Tamoxifen has been widely used for more than 30 years in breast cancer treatment and prevention. Tamoxifen acts mainly via estrogen receptors (ER), but also displays anti-tumor activity in breast cancer negative to ERs, suggesting other targets. Actually, tamoxifen has effects on several transduction pathways and diverse ion channels. Despite the successful use of tamoxifen, this drug produces some non-desirable side-effects by acting on different targets. However, such nonspecificity of tamoxifen might be used to unravel new targets to inhibit tumor cell proliferation, to elucidate new mechanisms of action of tamoxifen and tamoxifen analogs, and finally, to design new more specific and potent drugs on the benefit of cancer patients. This review will briefly describe first the current and general aspects of tamoxifen and then will focus more deeply on various tamoxifen analogues and new uses of tamoxifen described in recent patents. We will describe the biological effects and the therapeutic targets of the new patented analogues, in order to offer an alternative panorama on tamoxifen-based chemotherapy.
Keywords: Breast cancer, estrogen receptor, gene expression, ion channels, tamoxifen, tamoxifen derivatives, tamoxifen patents, Selective Estrogen Receptor Modulator, Triphenylethylenes, Benzothiophenes