Resistance to Aromatase Inhibitors in Breast Cancer

Aromatase Inhibitors (AIs) treat postmenopausal estrogen receptor positive tumours, which constitute the majority of breast cancer patients. The second section provides the detailed mechanisms of resistance to AIs, while the third section explores prediction of resistance and potential strategies to overcome resistance.

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.