Journal
CANCER SCIENCE
Volume 112, Issue 2, Pages 803-814Publisher
WILEY
DOI: 10.1111/cas.14769
Keywords
anaplastic thyroid cancer; combination therapy; polo‐ like kinase; sorafenib; volasertib
Categories
Funding
- Chang Gung Memorial Hospital, Linkou [CMRPG3H0201, CMRPG3E0353]
- National Institutes of Health [P30 CA008748]
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The PLK inhibitor volasertib has shown potential therapeutic effects in the treatment of anaplastic thyroid cancer (ATC), either alone or in combination with sorafenib. It decreases cell viability, induces apoptosis, and exhibits mostly synergistic effects in ATC cells, suggesting it could be an effective drug for treating ATC.
Polo-like kinases (PLKs) are potent regulators of cell proliferation and cell survival. Polo-like kinases are potential targets in the treatment of anaplastic thyroid cancer (ATC), a rare but deadly disease. The therapeutic effects of volasertib, a PLK inhibitor, was evaluated for the treatment of ATC either alone or in combination with sorafenib. Volasertib decreased cell viability in three ATC cell lines (8505C, 8305C, and KAT18) in a dose-dependent manner. Volasertib caused ATC cells to accumulate in G(2)/M phase, activated caspase-3 activity, and induced apoptosis. Combination therapy using volasertib and sorafenib in ATC cells showed mostly synergistic effects. In vivo studies revealed that combination therapy of volasertib and sorafenib was effective in the treatment of 8505C xenografts. Single-agent volasertib treatment was sufficient to retard 8305C tumor growth. No substantial morbidity was observed in animals that received either single-agent or combination treatment. These preclinical findings suggest that volasertib could be an effective drug in treating ATC.
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