title: Cell cycle proteins as promising targets in cancer therapy.
abstract: Cancer is characterized by uncontrolled tumour cell proliferation resulting from aberrant activity of various cell cycle proteins. Therefore, cell cycle regulators are considered attractive targets in cancer therapy. Intriguingly, animal models demonstrate that some of these proteins are not essential for proliferation of non-transformed cells and development of most tissues. By contrast, many cancers are uniquely dependent on these proteins and hence are selectively sensitive to their inhibition. After decades of research on the physiological functions of cell cycle proteins and their relevance for cancer, this knowledge recently translated into the first approved cancer therapeutic targeting of a direct regulator of the cell cycle. In this Review, we focus on proteins that directly regulate cell cycle progression (such as cyclin-dependent kinases (CDKs)), as well as checkpoint kinases, Aurora kinases and Polo-like kinases (PLKs). We discuss the role of cell cycle proteins in cancer, the rationale for targeting them in cancer treatment and results of clinical trials, as well as the future therapeutic potential of various cell cycle inhibitors.
authors.affiliation: Department of Cancer Biology, Dana-Farber Cancer Institute and Department of Genetics, Harvard Medical School, Boston, Massachusetts 02215, USA.|Department of Internal Medicine III, University Hospital RWTH Aachen, 52074 Aachen, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Otto
authors.affiliation: Department of Cancer Biology, Dana-Farber Cancer Institute and Department of Genetics, Harvard Medical School, Boston, Massachusetts 02215, USA.
authors.forename: Piotr
authors.initials: P
authors.lastname: Sicinski
mesh_terms: D000818:Animals; D064096:Aurora Kinase A / Q000037:antagonists & inhibitors / Q000502:physiology; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors* / Q000502:physiology; D000071877:Checkpoint Kinase 1 / Q000037:antagonists & inhibitors / Q000502:physiology; D002986:Clinical Trials as Topic; D051357:Cyclin-Dependent Kinase 2 / Q000037:antagonists & inhibitors / Q000502:physiology; D051358:Cyclin-Dependent Kinase 4 / Q000037:antagonists & inhibitors / Q000502:physiology; D051361:Cyclin-Dependent Kinase 6 / Q000037:antagonists & inhibitors / Q000502:physiology; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000502:physiology; D015398:Signal Transduction; D000097869:Polo-Like Kinase 1
chemical_list: D064096:Aurora Kinase A; D018797:Cell Cycle Proteins; D000071877:Checkpoint Kinase 1; D051357:Cyclin-Dependent Kinase 2; D051358:Cyclin-Dependent Kinase 4; D051361:Cyclin-Dependent Kinase 6; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins; D000097869:Polo-Like Kinase 1; C499349:WEE1 protein, human