title: The roles and therapeutic potential of cyclin-dependent kinases (CDKs) in sarcoma.
abstract: Uncontrolled proliferation and cell growth is the hallmark of many different malignant diseases, including sarcomas. Cyclin-dependent kinases (CDKs) are members of the serine/threonine protein kinase family and play crucial roles in tumor cell proliferation and growth by controlling cell cycle, transcription, and RNA splicing. In addition, several CDKs influence multiple targets and phosphorylate transcription factors involved in tumorigenesis. There are many examples linking dysregulated activation and expression of CDKs to tumors, and targeting CDKs in tumor cells has become a promising therapeutic strategy. More recently, the Food and Drug Administration (FDA) has approved the CDK4/6 inhibitor palbociclib for treating metastatic breast cancer. In sarcomas, high levels of CDK mRNA and protein expression have been found in most human sarcoma cells and patient tissues. Many studies have demonstrated consistent results in which inhibition of different CDKs decrease sarcoma cell growth and induce apoptosis. Therefore, CDKs comprise an attractive set of targets for novel anti-sarcoma drug development. In this review, we discuss the roles of different members of CDKs in various sarcomas and provide a pre-clinical overview of promising therapeutic potentials of targeting CDKs with a special emphasis on sarcoma.
authors.affiliation: Department of Orthopaedic Surgery, Sarcoma Biology Laboratory, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Jackson 1115, Boston, MA, 02114, USA.|Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jie Fang Avenue, Wuhan, China, 430022.
authors.forename: Yunfei
authors.initials: Y
authors.lastname: Liao
authors.affiliation: Department of Orthopaedic Surgery, Sarcoma Biology Laboratory, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Jackson 1115, Boston, MA, 02114, USA.|Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jie Fang Avenue, Wuhan, China, 430022.
authors.forename: Yong
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Department of Orthopaedic Surgery, Sarcoma Biology Laboratory, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Jackson 1115, Boston, MA, 02114, USA.
authors.forename: Jacson
authors.initials: J
authors.lastname: Shen
authors.affiliation: Department of Orthopaedic Surgery, Sarcoma Biology Laboratory, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Jackson 1115, Boston, MA, 02114, USA.
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Hornicek
authors.affiliation: Department of Orthopaedic Surgery, Sarcoma Biology Laboratory, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Jackson 1115, Boston, MA, 02114, USA. zduan@mgh.harvard.edu.
authors.forename: Zhenfeng
authors.initials: Z
authors.lastname: Duan
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D058990:Molecular Targeted Therapy; D005810:Multigene Family; D010766:Phosphorylation; D011485:Protein Binding; D047428:Protein Kinase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D012509:Sarcoma / Q000188:drug therapy / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D018844:Cyclin-Dependent Kinases
keywords: Cyclin-dependent kinase; Kinase inhibitor; Sarcoma; Targeted therapy