title: Why (multi)targeting of cyclin-dependent kinases is a promising therapeutic option for hormone-positive breast cancer and beyond.
abstract: Estrogens, via induction of their specific receptors (e.g., ER-α), regulate cell proliferation, differentiation and morphogenesis in mammary epithelium. Cell-cycle progression is driven by activation of complexes consisting of cyclin-dependent kinases (CDKs) and cyclins, which also modulate the activity of ER-α. Loss of control over the cell-cycle results in accelerated cell division and malignant transformation. Thus, a reciprocal relation exists between estrogen signaling and cell proliferation. Based on these findings, a new concept was developed to reduce ER-α activity and bring the cell cycle in transformed cells to heel. Prevention of ER-α activation and control over the deregulated cell cycle was achieved by supplementation with pharmacological CDK inhibitors alone or in combination with selective antiestrogens.
authors.affiliation: Cell Cycle Regulation Group, Department of Medicine, Div: Institute of Cancer Research, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
authors.forename: Józefa
authors.initials: J
authors.lastname: Węsierska-Gądek
authors.affiliation: Cell Cycle Regulation Group, Department of Medicine, Div: Institute of Cancer Research, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
authors.forename: Matthias
authors.initials: M
authors.lastname: Mauritz
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D005260:Female; D006801:Humans; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D047628:Estrogen Receptor alpha; D047428:Protein Kinase Inhibitors; D018844:Cyclin-Dependent Kinases