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Primary cell cultures for the personalized therapy in aggressive thyroid cancer of follicular origin
Seminars in Cancer Biology ( IF 12.1 ) Pub Date : 2020-06-20 , DOI: 10.1016/j.semcancer.2020.06.013
Poupak Fallahi 1 , Silvia Martina Ferrari 2 , Giusy Elia 2 , Francesca Ragusa 2 , Armando Patrizio 2 , Sabrina Rosaria Paparo 2 , Gianni Marone 3 , Maria Rosaria Galdiero 4 , Giovanni Guglielmi 1 , Rudy Foddis 1 , Alfonso Cristaudo 1 , Alessandro Antonelli 2
Affiliation  

Thyroid cancer (TC) is the most prevalent endocrine malignancy. More than 90 % of TC is represented by differentiated TC (DTC) arising from the follicular thyroid cells. DTC includes papillary TC (PTC), follicular TC (FTC), and Hürthle cell TC. Anaplastic TC (ATC) accounts for 1% of TC, and it represents 15–40 % of TC death. Current treatment strategies are not completely effective against aggressive DTC or ATC, and mortality is one of the most important challenges.

Recently, progresses have been obtained in the understanding of the molecular/genetic basis of TC progression, and new drugs have been introduced [i.e. tyrosine kinase inhibitors (TKIs)], able to block the oncogenic or signaling kinases, associated with cellular growth.

Thyroid cell lines, obtained from tumoral cells and chosen for high proliferation in vitro, have been used as preclinical models. Actually, these cells lose the characteristic features of the primary tumor, because they adapt to in vitro growth conditions. For these reasons, the use of these cell lines has important limitations, and more recently human primary cell cultures have been established as monolayer cultures, and investigated for their biological behavior. Moreover, in the past, primary TC cells could be collected only through surgical biopsies, while recently human primary cell cultures can be established also from samples of fine-needle aspiration citology from aggressive dedifferentiated DTC or ATC. Testing in vitro different TKIs in each patient can help to develop new personalized treatments, without using ineffective drugs.

In conclusion, personalized medicine and precise oncology, which consider both patients and their disease features, represent the future of the treatment approach, and further progress is needed in this direction.



中文翻译:

原代细胞培养用于滤泡性侵袭性甲状腺癌的个性化治疗

甲状腺癌(TC)是最常见的内分泌恶性肿瘤。超过 90% 的 TC 由甲状腺滤泡细胞产生的分化 TC (DTC) 代表。DTC 包括乳头状 TC (PTC)、滤泡状 TC (FTC) 和 Hürthle 细胞 TC。间变性 TC (ATC) 占 TC 的 1%,占 TC 死亡的 15-40%。目前的治疗策略对侵袭性 DTC 或 ATC 并不完全有效,死亡率是最重要的挑战之一。

最近,在了解 TC 进展的分子/遗传基础方面取得了进展,并且引入了能够阻断与细胞生长相关的致癌或信号激酶的新药物 [即酪氨酸激酶抑制剂 (TKI)]。

从肿瘤细胞中获得并选择用于体外高增殖的甲状腺细胞系已被用作临床前模型。实际上,这些细胞失去了原发性肿瘤的特征,因为它们适应了体外生长条件。由于这些原因,这些细胞系的使用具有重要的局限性,最近人类原代细胞培养物已被建立为单层培养物,并研究了它们的生物学行为。此外,在过去,原代 TC 细胞只能通过手术活检收集,而最近人类原代细胞培养物也可以从来自侵袭性去分化 DTC 或 ATC 的细针抽吸细胞学样本中建立。体外测试每个患者的不同 TKI 可以帮助开发新的个性化治疗,而无需使用无效的药物。

总之,考虑患者及其疾病特征的个性化医疗和精准肿瘤学代表了治疗方法的未来,需要在这个方向上取得进一步进展。

更新日期:2020-06-20
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