Targeting PLKs as a therapeutic approach to well-differentiated thyroid cancer. Issue 8 (August 2019)

• Record Type: Journal Article
• Authors: Lin, Shu-Fu; Lin, Jen-Der; Yeh, Chun-Nan; Huang, Yu-Tung; Chou, Ting-Chao; Wong, Richard J
• Is Part Of: Endocrine-related cancer. Volume 26:Issue 8(2019)
• Page Start: 727
• Page End: 738
• Publication Date: 2019-08
• Subjects: volasertib -- polo-like kinase inhibitor -- sorafenib -- well-differentiated thyroid cancer; Endocrine glands -- Cancer -- Periodicals; Endocrinology -- Periodicals; Cancer -- Endocrine aspects -- Periodicals; 616.9944005
• DOI: 10.1530/ERC-18-0555
• Languages: English
• ISSNs: 1351-0088

Abstract

Abstract : Polo-like kinases (PLKs) are pivotal regulators of cell proliferation and cell survival; therefore, PLKs may be potential targets in the treatment of malignancy. The therapeutic effects of volasertib, a PLKs inhibitor for papillary and follicular thyroid cancer (known as well-differentiated thyroid cancer (WDTC)), were evaluated in this study. Volasertib inhibited cell proliferation in two papillary and two follicular thyroid cancer cell lines in a dose-dependent manner. Volasertib treatment reduced cells in the S phase and increased cells in the G2/M phase. Volasertib activated caspase-3 activity and induced apoptosis. Drug combinations of volasertib and sorafenib showed mostly synergism in four well-differentiated thyroid carcinoma cell lines in vitro . Volasertib treatment in vivo retarded the growth of a papillary thyroid tumor model. Furthermore, the combination of volasertib with sorafenib was more effective than a single treatment of either in a follicular thyroid cancer xenograft model. Promising safety profiles appeared in animals treated with either volasertib alone or volasertib and sorafenib combination therapy. These findings support volasertib as a potential drug for the treatment of patients with WDTC.