Anticancer Drug Conjugates Incorporating Estrogen Receptor Ligands

Hormone-dependent cancers, such as certain types of breast cancer are characterized by over-expression of estrogen receptors (ERs). Anticancer drug conjugates combining ER ligands with other classes of anticancer agents may not only benefit from dual action at both anti-cancer targets but also from selective delivery of cytotoxic agents to ER-positive tumor cells resulting in less toxicity and adverse effects. Moreover, they could also take advantage of overcoming resistance typical for anti-hormonal monotherapy such as tamoxifen. In this review, we discuss the design, structures and pharmacological effects of numerous series of drug conjugates containing ER ligands such as selective ER modulators (tamoxifen, 4-hydroxytamoxifen, endoxifen), selective ER degraders (ICI-164384) and ER agonists (estradiol) linked to diverse anti-cancer agents including histone-deacetylase inhibitors, DNA-alkylating agents, antimitotic agents and epidermal growth factor receptor inhibitors.

Automated summary

Hormone-dependent cancers, such as certain types of breast cancer, can be treated with anticancer drug conjugates that combine estrogen receptor (ER) ligands with other anticancer agents. These conjugates not only have dual action at anti-cancer targets, but also selectively deliver cytotoxic agents to ER-positive tumor cells, reducing toxicity and adverse effects. They can also overcome resistance to anti-hormonal monotherapy. This review discusses the design, structures, and pharmacological effects of various drug conjugates containing ER ligands linked to diverse anticancer agents.