A major challenge in cancer research is the discovery of drugs with high
selectivity and only minor side effects. Tamoxifen has been widely used for more than
30 years in breast cancer treatment and prevention, and it acts primarily via oestrogen
receptors (ERs). However, it also displays anti-tumour activity in ER-negative breast
cancer, suggesting that tamoxifen targets other proteins. Indeed, tamoxifen has effects
on several signal transduction pathways and ion channels, which are involved in tumor
progression; these targets of tamoxifen with antitumor potential can be targeted in the
search for more effective drugs. Despite the successful use of tamoxifen, it produces
some undesirable side effects by acting on different targets, many of which have not
been clarified. Thus, several strategies have been proposed to increase the effectiveness
of tamoxifen. These strategies include the synthesis of compounds with chemical
structures analogous to tamoxifen as well as different routes of administration for this
group of compounds and the use of tamoxifen in combination with other antineoplastic
drugs. This chapter will first briefly describe the current and general aspects of
tamoxifen and will then focus more in depth on various patented analogues, patented
uses of tamoxifen, and patented combinations of tamoxifen with other antineoplastic
drugs. We also discuss the biological effects of tamoxifen and its therapeutic targets.
This chapter provides an updated look at current tamoxifen-based therapies and new
strategies for using tamoxifen to benefit cancer patients.
Keywords: Agonist, antagonist, benzopyrans, benzothiophenes, breast cancer,
cytochrome P450 enzyme complex, CYP2D6, CYP3A4, FDA, gene expression,
indoles, ion channels, oestrogen receptors, selective oestrogen modulators,
tamoxifen, tamoxifen derivatives, tamoxifen metabolites, tamoxifen patents,
tetrahydronaphthalenes, triphenylethylenes.
