Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Department of Emergency Medicine, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.
Expert Opin Pharmacother. 2024 Aug;25(12):1667-1676. doi: 10.1080/14656566.2024.2393281. Epub 2024 Aug 28.
Oncogenic tyrosine kinases (TK) are enzymes that play a key role in cell growth and proliferation and their mutations can lead to uncontrolled cell growth and development of aggressive cancer. This knowledge has led to the development of new classes of drugs, Tyrosine kinase inhibitors (TKI). They target oncogenic kinases who are associated with advanced radioactive iodine (RAI) refractory TC, which is not able to uptake RAI anymore and/or still grows between consecutive treatments with Iodine 131 (I131).
Since Lenvatinib and Sorafenib approval, several other molecular inhibitors have been studied and then introduced for the treatment of aggressive and refractory thyroid cancer (TC), and, although the development of adverse effects or tumor resistance mechanisms, more and more compounds are still under investigation. The literature search was executed in PubMed and ClinicalTrials.gov to identify relevant articles and clinical trials published until December 2023.
In the context of clinical trials, driven by the presence of specific molecular mutations or even in the absence of both conditions, systemic therapy TKIs are valuable weapons to be used in patients affected by aggressive forms of TC, waiting for further expansion of the treatment landscape with more efficacious and safer drugs.
致癌酪氨酸激酶(TK)是在细胞生长和增殖中起关键作用的酶,其突变可导致不受控制的细胞生长和侵袭性癌症的发展。这一知识促使开发了新的药物类别,即酪氨酸激酶抑制剂(TKI)。它们靶向与放射性碘(RAI)难治性 TC 相关的致癌激酶,这些 TC 不再能够摄取 RAI,并且/或者在连续用碘 131(I131)治疗之间仍在生长。
自仑伐替尼和索拉非尼获得批准以来,已经研究了其他几种分子抑制剂,并将其引入侵袭性和难治性甲状腺癌(TC)的治疗中,尽管出现了不良反应或肿瘤耐药机制,但仍有越来越多的化合物在进行研究。在 PubMed 和 ClinicalTrials.gov 中进行了文献检索,以确定截至 2023 年 12 月发表的相关文章和临床试验。
在临床试验的背景下,由于存在特定的分子突变,甚至在没有这两种情况的情况下,系统治疗 TKI 是用于治疗侵袭性 TC 患者的有价值的武器,等待更有效和更安全的药物进一步扩大治疗范围。