title: Targeting CDK6 in cancer: State of the art and new insights.
abstract: Cyclin-dependent kinase 6 (CDK6) plays a vital role in regulating the progression of the cell cycle. More recently, CDK6 has also been shown to have a transcriptional role in tumor angiogenesis. Up-regulated CDK6 activity is associated with the development of several types of cancers. While CDK6 is over-expressed in cancer cells, it has a low detectable level in non-cancerous cells and CDK6-null mice develop normally, suggesting a specific oncogenic role of CDK6, and that its inhibition may represent an ideal mechanism-based and low toxic therapeutic strategy in cancer treatment. Identification of selective small molecule inhibitors of CDK6 is thus needed for drug development. Herein, we review the latest understandings of the biological regulation and oncogenic roles of CDK6. The potential clinical relevance of CDK6 inhibition, the progress in the development of small-molecule CDK6 inhibitors and the rational design of potential selective CDK6 inhibitors are also discussed.
authors: a Center for Drug Discovery and Development, Sansom Institute for Health Research, Center for Cancer Biology; and School of Pharmacy and Medical Sciences, University of South Australia ; Adelaide , Australia.
authors: Solomon
authors: S
authors: Tadesse
authors: a Center for Drug Discovery and Development, Sansom Institute for Health Research, Center for Cancer Biology; and School of Pharmacy and Medical Sciences, University of South Australia ; Adelaide , Australia.
authors: Mingfeng
authors: M
authors: Yu
authors: a Center for Drug Discovery and Development, Sansom Institute for Health Research, Center for Cancer Biology; and School of Pharmacy and Medical Sciences, University of South Australia ; Adelaide , Australia.
authors: Malika
authors: M
authors: Kumarasiri
authors: a Center for Drug Discovery and Development, Sansom Institute for Health Research, Center for Cancer Biology; and School of Pharmacy and Medical Sciences, University of South Australia ; Adelaide , Australia.
authors: Bich Thuy
authors: BT
authors: Le
authors: a Center for Drug Discovery and Development, Sansom Institute for Health Research, Center for Cancer Biology; and School of Pharmacy and Medical Sciences, University of South Australia ; Adelaide , Australia.
authors: Shudong
authors: S
authors: Wang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology; D018360:Crystallography, X-Ray; D051361:Cyclin-Dependent Kinase 6 / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D016503:Drug Delivery Systems / Q000379:methods / Q000639:trends*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D017433:Protein Structure, Secondary
chemical_list: D000970:Antineoplastic Agents; C495911:CDK6 protein, human; D051361:Cyclin-Dependent Kinase 6
keywords: cell cycle; cyclin-dependent kinase; drug discovery; inhibitor design; oncogene and tumor suppressor; targeted cancer therapy