Department of Internal Medicine, University of Pisa School of Medicine, Via Roma, 67, I-56100, Pisa, Italy.
Anticancer Agents Med Chem. 2012 Jan;12(1):87-93. doi: 10.2174/187152012798764732.
Anaplastic thyroid cancer (ATC) is often incurable because it doesn't respond to radioiodine, radiotherapy or chemotherapy, and new therapeutic approaches are needed. Peroxisome proliferator-activated receptor-gamma (PPARg) gene and protein are present in ATC cells, and PPARg ligands inhibit cell proliferation, induce apoptosis, and also down regulate the invasive potential of ATC cells. Also, inhibitors of the Aurora serine/threonine kinases have antineoplastic effect on ATC cells in vitro and on ATC xenografts. Tyrosine kinases inhibitors are actually under evaluation for the treatment of ATC, for example imanitib or sorafenib. Other studies have focused on evaluating antiangiogenic agents for treatment of ATC. These agents include: combretastatin A4 phosphate, aplidin, PTK787/ZK222584, and human VEGF monoclonal antibodies (bevacizumab, cetuximab). Small-molecule adenosine triphosphate (ATP) competitive inhibitors directed intracellularly at epidermal growth factor receptor (EGFR)'s tyrosine kinase, such as erlotinib, or gefitinib are also under evaluation. The development of drugs that have multiple therapeutic targets and the utilization of multiple cancer-targeting agents are both emerging strategies for ATC treatment. For example, a preclinical study evaluated the activity of a dual inhibitor of EGFR and vascular endothelial growth factor (VEGF), NVP-AEE788, alone and in combination with paclitaxel for the treatment of ATC. Even if new therapeutic approaches against ATC are under development, more research is needed to finally identify therapies able to control and to cure this disease. The possibility of testing the sensitivity of primary ATC cells from each subject to different drugs could increase the effectiveness of the treatment in the next future.
间变性甲状腺癌（ATC）通常无法治愈，因为它对放射性碘、放疗或化疗没有反应，因此需要新的治疗方法。过氧化物酶体增殖物激活受体-γ（PPARγ）基因和蛋白存在于 ATC 细胞中，PPARγ 配体抑制细胞增殖，诱导细胞凋亡，并下调 ATC 细胞的侵袭潜力。此外，Aurora 丝氨酸/苏氨酸激酶抑制剂在体外和 ATC 异种移植物中对 ATC 细胞具有抗肿瘤作用。酪氨酸激酶抑制剂实际上正在评估用于治疗 ATC，例如伊马替尼或索拉非尼。其他研究集中在评估抗血管生成剂用于治疗 ATC。这些药物包括：combretastatin A4 磷酸盐、aplidin、PTK787/ZK222584 和人 VEGF 单克隆抗体（bevacizumab、cetuximab）。针对表皮生长因子受体（EGFR）酪氨酸激酶的细胞内小分子三磷酸腺苷（ATP）竞争性抑制剂，如厄洛替尼或吉非替尼，也在评估中。具有多个治疗靶点的药物的开发和多种癌症靶向药物的利用都是 ATC 治疗的新兴策略。例如，一项临床前研究评估了 EGFR 和血管内皮生长因子（VEGF）双重抑制剂 NVP-AEE788 单独使用和联合紫杉醇治疗 ATC 的活性。即使针对 ATC 的新治疗方法正在开发中，仍需要更多的研究最终确定能够控制和治愈这种疾病的治疗方法。测试每个患者的原发性 ATC 细胞对不同药物的敏感性的可能性，可以提高未来治疗的效果。
