Department of Internal Medicine, New Taipei Municipal TuCheng Hospital, New Taipei City, Taiwan.
Department of Internal Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
Cancer Sci. 2021 Feb;112(2):803-814. doi: 10.1111/cas.14769. Epub 2021 Jan 2.
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 /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.
丝氨酸/苏氨酸激酶（PLKs）是细胞增殖和细胞存活的有力调节剂。PLKs 是治疗间变性甲状腺癌（ATC）的潜在靶点，ATC 是一种罕见但致命的疾病。PLK 抑制剂 Volasertib 单独或与索拉非尼联合用于治疗 ATC 的疗效进行了评估。Volasertib 以剂量依赖性方式降低三种 ATC 细胞系（8505C、8305C 和 KAT18）的细胞活力。Volasertib 导致 ATC 细胞在 G/M 期积累，激活 caspase-3 活性并诱导细胞凋亡。在 ATC 细胞中使用 Volasertib 和索拉非尼的联合治疗显示出主要的协同作用。体内研究表明，Volasertib 和索拉非尼的联合治疗对 8505C 异种移植物的治疗有效。单药 Volasertib 治疗足以延缓 8305C 肿瘤的生长。接受单一药物或联合治疗的动物未观察到明显的发病率。这些临床前研究结果表明，Volasertib 可能是治疗 ATC 的有效药物。
