Targeting tumors using estrogen receptor ligand conjugates.
When treating cancer, cytotoxic agents are intended to exert their effect on rapidly proliferating cancer cells. However, often cancer chemotherapies lack specificity which can lead to toxicity and undesirable side affects. Many approaches have been designed to target tumors. Selective chemotherapies can be established by focusing on distinctive physiological, morphological and environmental differences between tumor and healthy tissue. For example, agents targeting nuclear receptors over-expressed in tumors can hone in on malignant tissue and result in improved chemotherapeutic treatments. In hormone-dependent cancers, such as certain breast cancers, a number of structurally varied estrogen receptor ligand conjugates have been investigated attempting to take advantage of the presence of over-expressed estrogen receptor. Estrogen receptor ligand conjugates containing a variety of cytotoxic agents, photodynamic therapeutic agents and radioligands have been reported. In addition, studies to improve the pharmaceutical properties of certain estrogen receptor ligand conjugates have shown promising results. In this review, developments in these specific types of estrogen receptor targeting approaches are discussed which highlight the potential advantages of these conjugates in the discovery of more effective cancer chemotherapy agents.
School of Pharmacy and Pharmaceutical Sciences, Panoz Institute, Trinity College, Dublin 2, Ireland.
N O
NO
Keely
M J
MJ
Meegan
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001665:Binding Sites; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D015195:Drug Design; D004958:Estradiol / Q000031:analogs & derivatives / Q000627:therapeutic use; D020847:Estrogen Receptor Modulators / Q000378:metabolism / Q000627:therapeutic use; D005260:Female; D000077267:Fulvestrant; D006801:Humans; D008024:Ligands; D009367:Neoplasm Staging; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D011960:Receptors, Estrogen / Q000187:drug effects / Q000378:metabolism*
D000970:Antineoplastic Agents; D020847:Estrogen Receptor Modulators; D008024:Ligands; D011960:Receptors, Estrogen; D000077267:Fulvestrant; D004958:Estradiol