Ferrari Silvia Martina, La Motta Concettina, Elia Giusy, Ragusa Francesca, Ruffilli Ilaria, Quattrini Luca, Paparo Sabrina Rosaria, Piaggi Simona, Patrizio Armando, Ulisse Salvatore, Baldini Enke, Materazzi Gabriele, Fallahi Poupak, Antonelli Alessandro
Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Department of Pharmacy, University of Pisa, Pisa, Italy.
Front Endocrinol (Lausanne). 2018 Dec 18;9:764. doi: 10.3389/fendo.2018.00764. eCollection 2018.
Anaplastic thyroid carcinoma (ATC) is a malignant tumor of the thyroid gland, infrequent but with a very poor prognosis, as it rapidly causes death (mean survival of about 6 months). ATC treatment includes a multimodal protocol consisting of surgery, chemotherapy (doxorubicin and cisplatin), and hyperfractionated accelerated external beam radiotherapy (median patient survival of 10 months). For this reason, the identification of an effective systemic treatment for ATC would be a major advance in the management of this deadly thyroid cancer. The opportunity to test the sensitivity to different drugs of primary cells from ATC (pATC) cultures, obtained from each patients, could improve the effectiveness of the treatment. Then, the administration of inactive therapeutics could be avoided. Our aim is to investigate the antineoplastic effect of two tyrosine kinase inhibitors (TKIs; lenvatinib, vandetanib) in pATC obtained both from biopsy (biop-pATC), and from fine needle aspiration (FNA-pATC). The antiproliferative activity of lenvatinib and vandetanib was evaluated in 6 ATC patients, on biop-pATC, such as on FNA-pATC. A significant reduction of proliferation (obtained by WST-1 assay) vs. control was shown with lenvatinib and vandetanib in FNA-pATC, as well as in biop-pATC. The percentage of apoptosis in FNA-pATC, or biop-pATC, increased with both compounds dose-dependently. pATC cells from FNA, or biopsy, had a similar sensitivity to lenvatinib and vandetanib. In conclusion, primary cells (biop-pATC or FNA-pATC) have a similar sensitivity to TKIs, and lenvatinib and vandetanib are effective in reducing cell growth, increasing apoptosis in ATC. The possibility to test the sensitivity to different TKIs in each patient could open the way to personalized treatments, avoiding the administration of ineffective, and potentially dangerous, drugs.
间变性甲状腺癌（ATC）是一种甲状腺恶性肿瘤，虽不常见但预后极差，因为它会迅速导致死亡（平均生存期约6个月）。ATC的治疗包括一个多模式方案，由手术、化疗（阿霉素和顺铂）以及超分割加速外照射放疗组成（患者中位生存期为10个月）。因此，确定一种有效的ATC全身治疗方法将是这种致命性甲状腺癌治疗管理方面的一项重大进展。检测从每位患者获取的ATC原代细胞（pATC）培养物对不同药物的敏感性，可能会提高治疗效果。这样就能避免使用无效的治疗药物。我们的目的是研究两种酪氨酸激酶抑制剂（TKIs；乐伐替尼、凡德他尼）对从活检（活检-pATC）和细针穿刺活检（FNA-pATC）获取的pATC的抗肿瘤作用。在6例ATC患者中，对活检-pATC以及FNA-pATC评估了乐伐替尼和凡德他尼的抗增殖活性。在FNA-pATC以及活检-pATC中，乐伐替尼和凡德他尼与对照相比，显示出增殖的显著降低（通过WST-1检测获得）。两种化合物均使FNA-pATC或活检-pATC中的凋亡百分比呈剂量依赖性增加。来自FNA或活检的pATC细胞对乐伐替尼和凡德他尼具有相似的敏感性。总之，原代细胞（活检-pATC或FNA-pATC）对TKIs具有相似的敏感性，乐伐替尼和凡德他尼可有效减少细胞生长，增加ATC中的凋亡。检测每位患者对不同TKIs的敏感性，有可能为个性化治疗开辟道路，避免使用无效且可能危险的药物。
