title: The Metabolism, Analysis, and Targeting of Steroid Hormones in Breast and Prostate Cancer.
abstract: Breast and prostate cancers are malignancies in which steroid hormones drive cellular proliferation. Over the past century, this understanding has led to successful treatment strategies aimed to inhibit hormone-mediated tumor growth. Nonetheless, disease relapse and progression still pose significant clinical problems, with recurrent and metastatic tumors often exhibiting resistance to current drug therapies. The central role of androgens and estrogens in prostate and breast cancer etiology explains not only why endocrine therapies are often initially successful but also why many tumors ultimately become resistant. It is hypothesized that reducing the concentration of active hormones in the systemic circulation may be insufficient to block cancer progression, as this action selects for tumor cells that can generate active steroids from circulating precursors. This review aims to highlight the currently known differences of steroid biosynthesis in normal physiology versus hormone-dependent cancers, modern approaches to the assessment and targeting of these pathways, and priorities for future research.
authors.affiliation: Division of Hematology/Oncology, Department of Internal Medicine and Department of Pharmacology, University of Michigan, Ann Arbor, MI, 48019, USA.
authors.forename: Cameron P
authors.initials: CP
authors.lastname: Capper
authors.affiliation: Division of Hematology/Oncology, Department of Internal Medicine and Department of Pharmacology, University of Michigan, Ann Arbor, MI, 48019, USA.
authors.forename: James M
authors.initials: JM
authors.lastname: Rae
authors.affiliation: Division of Metabolism, Diabetes, and Endocrinology, Department of Internal Medicine and Department of Pharmacology, University of Michigan School of Medicine, Room 5560A, MSRBII, 1150 W. Medical Center Drive, Ann Arbor, MI, 48019, USA. rauchus@med.umich.edu.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Auchus
mesh_terms: D000728:Androgens / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism*; D004967:Estrogens / Q000378:metabolism; D005260:Female; D006066:Gonads / Q000378:metabolism; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism; D008297:Male; D058990:Molecular Targeted Therapy; D009154:Mutation; D010913:Pituitary-Adrenal System / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013256:Steroids / Q000037:antagonists & inhibitors* / Q000378:metabolism*
chemical_list: D000728:Androgens; D000970:Antineoplastic Agents; D004967:Estrogens; D018160:Receptors, Cytoplasmic and Nuclear; D013256:Steroids