title: New directions for drug-resistant breast cancer: the CDK4/6 inhibitors.
abstract: Many breast cancers are treated with selective estrogen receptor modulators (SERMs) if the cancers are estrogen and progesterone hormone receptor positive. However, some 30% are not responsive or later become resistant to such therapies. There has been continued interest in developing new and more effective SERMs that target the estrogen receptors for therapeutic benefit. This article will focus on therapies directed against other molecular targets to improve outcomes, as preventing growth of breast cancer cells by an unrelated mechanism is most likely to yield success against resistance, or synergize in a combination therapy with SERMs or aromatase inhibitors. New drugs in development that target the cyclin-dependent kinases CDK4/CDK6 have 'breakthrough therapy' designation at the US FDA and may provide an exciting and realistic new avenue to patients in the near future.
authors: Department of Pharmacology & Chemical Biology, School of Medicine, University of Pittsburgh, 4200 Fifth Ave, Pittsburgh, PA 15260, USA.
authors: Mark
authors: M
authors: Nichols
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D047072:Aromatase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D001940:Breast / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D051358:Cyclin-Dependent Kinase 4 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051361:Cyclin-Dependent Kinase 6 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D055808:Drug Discovery; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D058990:Molecular Targeted Therapy; D047428:Protein Kinase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D047072:Aromatase Inhibitors; D047428:Protein Kinase Inhibitors; D020845:Selective Estrogen Receptor Modulators; C495900:CDK4 protein, human; C495911:CDK6 protein, human; D051358:Cyclin-Dependent Kinase 4; D051361:Cyclin-Dependent Kinase 6