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Many breast tumours are dependent upon oestrogen for their development and continued growth. Over the last 25 years hormone therapy has progressed from the irreversible destruction of endocrine glands to the use of drugs that reversibly suppress oestrogen synthesis or action. The inhibition of oestrogen synthesis is most readily achieved by inhibiting the final step in the pathway of oestrogen biosynthesis, the reaction which transforms androgens into oestrogens by creating an aromatic ring in the steroid molecule (hence the enzyme's trivial name, aromatase). Whereas the first aromatase inhibitors to be used therapeutically could be shown to produce drug-induced inhibition of the enzyme and therapeutic benefits in patients with breast cancer, they were not particularly potent and lacked specificity. However, second-generation drugs were developed and most recently third-generation inhibitors have evolved which possess remarkable specificity and potency. Initial results from clinical trials suggest that these agents will become the cornerstones of future endocrine therapy.

Breast --- Aromatase --- Cancer --- Chemotherapy. --- Inhibitors --- Therapeutic use. --- CYP19 (Enzyme) --- Cytochrome P-450 (Arom) --- Cytochrome P-450 CYP19 --- Cytochrome P-450 --- Oxidoreductases --- Oncology. --- Toxicology. --- Internal medicine. --- Oncology  . --- Cytology. --- Cancer Research. --- Pharmacology/Toxicology. --- Internal Medicine. --- Cell Biology. --- Medicine, Internal --- Medicine --- Chemicals --- Pharmacology --- Poisoning --- Poisons --- Tumors --- Cell biology --- Cellular biology --- Biology --- Cells --- Cytologists --- Toxicology --- Cancer research. --- Pharmacology. --- Cell biology. --- Drug effects --- Medical pharmacology --- Medical sciences --- Chemotherapy --- Drugs --- Pharmacy --- Cancer research --- Physiological effect

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The book brings together current knowledge about molecular and clinical aspects of resistance to aromatase inhibitors (AIs). The topics and features include: The history of development and clinical role of aromatase inhibitors in breast cancer. The structure and function of aromatase gene and protein, including tissue-specific splicing and regulation of the gene, crystal structure of the enzyme, functioning of its active site and structural basis for development of new aromatase inhibitors. Experimental and pre-clinical models of resistance to aromatase inhibitors (including cell lines and xenografts) as well as methods and results of measuring oestrogen concentrations in blood and tumour tissue of breast cancer patients. Diversity of molecular mechanisms of AI resistance, including (i) ligand-independent signalling through oestrogen receptor pathway, (ii) hypersensitivity to low concentrations of oestrogens, (iii) crosstalk with non-endocrine signalling (including PI3K/mTOR, IGF, GDNF and Myc pathways), (iv) involvement of oestrogen-induced apoptosis and tissue microenvironment (including inflammatory immune cells and adipocytes) as well as (v) the role of epigenetic mechanisms and pioneering factors in ER signalling and AI resistance. Molecular markers and multi-gene signatures to predict response to AIs, clinical trials aimed at preventing or overcoming resistance by combining AIs with novel targeted agents (including AI combinations with HER2, EGFR, mTOR, PI3K, Akt, CDK4/6, FGFR, HDAC, IGF-1, Src, proteosome- and angiogenic- targeting agents). A review of the effects and clinical indications of aromatase inhibitors beyond breast cancer. Many of the chapters provide extensive historical overviews to connect current knowledge with the history and inner logic of the field. The authors’ team includes world-leading experts, making the book an essential resource for scientists developing new treatments for breast cancer and for medics treating breast cancer patients with aromatase inhibitors.

Biomedicine. --- Cancer Research. --- Drug Resistance. --- Molecular Medicine. --- Medicine. --- Oncology. --- Drug interactions. --- Médecine --- Cancérologie --- Médicaments --- Interaction --- Medicine --- Health & Biological Sciences --- Oncology --- Breast --- Aromatase --- Estrogen --- Cancer --- Chemotherapy. --- Inhibitors --- Therapeutic use. --- Hormone therapy. --- Antagonists --- Oestrogen --- CYP19 (Enzyme) --- Cytochrome P-450 (Arom) --- Cytochrome P-450 CYP19 --- Cancer research. --- Drug resistance. --- Molecular biology. --- Hormones, Sex --- Anti-estrogenic diet --- Cytochrome P-450 --- Oxidoreductases --- Clinical sciences --- Medical profession --- Human biology --- Life sciences --- Medical sciences --- Pathology --- Physicians --- Interactions, Drug --- Drugs --- Tumors --- Side effects --- Health Workforce --- Molecular biochemistry --- Molecular biophysics --- Biochemistry --- Biophysics --- Biomolecules --- Systems biology --- Resistance to drugs --- Pharmacology --- Cancer research