title: Dysregulation of Aromatase in Breast, Endometrial, and Ovarian Cancers: An Overview of Therapeutic Strategies.
abstract: Aromatase is the rate-limiting enzyme in the biosynthesis of estrogens, which play crucial roles on a spectrum of developmental and physiological processes. The biological actions of estrogens are classically mediated by binding to two estrogen receptors (ERs), ERα and ERβ. Encoded by the cytochrome P450, family 19, subfamily A, polypeptide 1 (CYP19A1) gene, aromatase is expressed in a wide variety of tissues, as well as benign and malignant tumors, and is regulated in a pathway- and tissue-specific manner. Overexpression of aromatase, leading to elevated systemic levels of estrogen, is unequivocally linked to the pathogenesis and growth of a number malignancies, including breast, endometrium, and ovarian cancers. Aromatase inhibitors (AIs) are routinely used to treat estrogen-dependent breast cancers in postmenopausal women; however, their roles in endometrial and ovarian cancers remain obscure. While AI therapy is effective in hormone sensitive cancers, they diminish estrogen production throughout the body and, thus, generate undesirable side effects. Despite the effectiveness of AI therapy, resistance to endocrine therapy remains a major concern and is the leading cause of cancer death. Considerable advances, toward mitigating these issues, have evolved in conjunction with a number of histone deacetylase (HDAC) inhibitors for countering an assortment of diseases and cancers, including the aforesaid malignancies. HDACs are a family of enzymes that are frequently dysregulated in human tumors. This chapter will discuss the current understanding of aberrant regulation and expression of aromatase in breast, endometrial, and ovarian cancers, and potential therapeutic strategies for prevention and treatment of these life-threatening diseases.
authors.affiliation: Texas Tech University Health Sciences Center School of Medicine, Lubbock, TX, United States. Electronic address: pulak.manna@ttuhsc.edu.
authors.forename: P R
authors.initials: PR
authors.lastname: Manna
authors.affiliation: Texas Tech University Health Sciences Center School of Medicine, Lubbock, TX, United States.
authors.forename: D
authors.initials: D
authors.lastname: Molehin
authors.affiliation: Texas Tech University Health Sciences Center School of Medicine, Lubbock, TX, United States.
authors.forename: A U
authors.initials: AU
authors.lastname: Ahmed
mesh_terms: D001141:Aromatase / Q000378:metabolism*; D001943:Breast Neoplasms / Q000201:enzymology*; D016889:Endometrial Neoplasms / Q000201:enzymology*; D004967:Estrogens / Q000096:biosynthesis; D005260:Female; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006801:Humans; D010051:Ovarian Neoplasms / Q000201:enzymology*; D011960:Receptors, Estrogen / Q000378:metabolism
chemical_list: D004967:Estrogens; D056572:Histone Deacetylase Inhibitors; D011960:Receptors, Estrogen; D001141:Aromatase
keywords: AIs; Aromatase; CYP19A1; Estrogens; HDACs; Targeted therapy; Tumors/cancers