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Cancer and Metastasis Reviews

, Volume 35, Issue 2, pp 151–163 | Cite as

The roles and therapeutic potential of cyclin-dependent kinases (CDKs) in sarcoma

  • Yunfei Liao
  • Yong Feng
  • Jacson Shen
  • Francis J. Hornicek
  • Zhenfeng Duan
NON-THEMATIC REVIEW

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.

Keywords

Cyclin-dependent kinase Sarcoma Kinase inhibitor Targeted therapy 

Notes

Acknowledgments

This work was supported, in part, by the Gattegno and Wechsler funds, and the Kenneth Stanton Fund. Dr. Duan is supported, in part, through a grant from the Sarcoma Foundation of America (SFA); a grant from the National Cancer Institute (NCI)/National Institutes of Health (NIH), UO1, CA 151452–01; a pilot grant from Sarcoma SPORE/NIH; and a grant from an Academic Enrichment Fund of MGH Orthopaedics.

Compliance with ethical standards

Disclosure of potential conflicts of interest

No potential conflicts of interest were disclosed.

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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Yunfei Liao
    • 1
    • 2
  • Yong Feng
    • 1
    • 2
  • Jacson Shen
    • 1
  • Francis J. Hornicek
    • 1
  • Zhenfeng Duan
    • 1
  1. 1.Department of Orthopaedic Surgery, Sarcoma Biology LaboratoryMassachusetts General Hospital and Harvard Medical SchoolBostonUSA
  2. 2.Wuhan Union Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina

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