Activity of roniciclib in medullary thyroid cancer

Shu-Fu Lin; Jen-Der Lin; Chuen Hsueh; Ting-Chao Chou; Richard J. Wong

doi:10.18632/oncotarget.25555

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Research Papers:

Activity of roniciclib in medullary thyroid cancer

Shu-Fu Lin _, Jen-Der Lin, Chuen Hsueh, Ting-Chao Chou and Richard J. Wong

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Oncotarget. 2018; 9:28030-28041. https://doi.org/10.18632/oncotarget.25555

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Abstract

Shu-Fu Lin1, Jen-Der Lin1, Chuen Hsueh2, Ting-Chao Chou3,4 and Richard J. Wong5

1Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan

2Department of Pathology, Chang Gung Memorial Hospital, Taoyuan, Taiwan

3Laboratory of Preclinical Pharmacology Core, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

4Current address: PD Science, Inc., Paramus, NJ, USA

5Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

Correspondence to:

Shu-Fu Lin, email: [email protected]

Keywords: roniciclib; cyclin-dependent kinase; medullary thyroid cancer

Received: July 26, 2017 Accepted: May 21, 2018 Published: June 15, 2018

ABSTRACT

Altered cyclin-dependent kinase activity is observed in many human malignancies. Cyclin-dependent kinases that promote cell cycle progression may be promising targets in the treatment of cancer. The therapeutic effects of roniciclib, a cyclin-dependent kinase inhibitor for medullary thyroid cancer were investigated in the present study. Roniciclib inhibited medullary thyroid cancer cell proliferation in a dose-dependent manner. Roniciclib induced caspase-3 activity and contributed to apoptosis. Cell cycle progression was arrested in the G2 phase. In vivo, roniciclib treatment retarded the growth of tumors of medullary thyroid cancer xenografts. In addition, roniciclib in combination with sorafenib was more effective than either single treatment in a xenograft model. No morbidity was observed in animals treated with single roniciclib therapy and combination treatment of roniciclib and sorafenib. These data provide a rationale for clinical assessment of using roniciclib in the treatment of patients with medullary thyroid cancer.

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Research Papers:

Activity of roniciclib in medullary thyroid cancer

Abstract