■甲状腺髓样癌(MTC)是一种罕见的甲状腺肿瘤,其晚期治疗具有挑战性,尽管近年来有效的治疗选择已经扩大。蛋白酶体抑制剂(PrIn)已显示出改善患者预后的能力,包括生存和生活质量,在几个恶性肿瘤中,由于它们通过抑制蛋白酶体活性而损害细胞增殖并引起细胞凋亡的能力。因此,这些药物可能是一个有用的工具,单独或与其他治疗相结合,在MTC患者中。
■这篇综述旨在总结有关PrIn在MTC中的作用的体外和体内可用数据。
■我们对相关数据源进行了广泛的搜索,包括国际在线数据库中完整发表的文章(PubMed,WebofScience,Scopus),选定的国际会议摘要存储库中的初步报告,以及作为国际会议增刊发表的短文,使用以下术语:甲状腺髓样癌,蛋白酶体抑制剂,硼替佐米,Carfilzomib,艾沙佐米,Delanzomib,marizomib,奥普佐米,MG132。此外,我们用相同的关键词进行,在注册临床试验存储库中进行深入搜索。
■我们的搜索揭示了人和鼠MTC细胞系的体外研究,基于Prins的使用,单独或与其他抗癌药物联合使用,和两项相关的临床试验。
■我们发现临床前研究中PrIns效应的证据之间存在很大差异,以及临床试验的稀缺性或早期中断。我们可能会推测招募病人的困难,就像其他罕见疾病一样,可能阻碍了试验的实施,支持已经批准用于MTC的药物。然而,鉴于对MTC中PrIn效应的分子基础的理解有了具体的改进,具有准确纳入标准的新临床试验可能是必要的,为了确定这种治疗,单独或与其他药物联合使用,确实可以代表一种增强治疗反应的选择,并最终改善患者的预后和生存率。
Medullary thyroid cancer (MTC) is a rare thyroid tumour whose management in advanced stages is challenging, despite effective therapeutic options having expanded in recent years. Proteasome inhibitors (PrIn) have shown the ability to improve patient outcomes, including survival and quality of life, in several malignancies, due to their ability to impair cell proliferation and cause apoptosis through the inhibition of the proteasome activity. Consequently, these drugs could represent a useful tool, alone or in combination with other treatments, in MTC patients.
This review aims to summarize the available in vitro and in vivo data about the role of PrIn in MTC.
We performed an extensive search for relevant data sources, including full-published articles in international online databases (PubMed, Web of Science, Scopus), preliminary reports in selected international meeting abstract repositories, and short articles published as supplements of international meetings, by using the following terms: medullary thyroid carcinoma, proteasome inhibitors, bortezomib, carfilzomib, ixazomib, delanzomib, marizomib, oprozomib, and
MG132. Additionally, we conducted with the same keywords, an in-depth search in registered clinical trials repositories.
Our search revealed in vitro studies in human and murine MTC cell lines, based on the use of PrIns, both alone and in combination with other anticancer drugs, and two pertinent clinical trials.
We found a strong discrepancy between the evidence of PrIns effects in preclinical studies, and the scarcity or early interruption of clinical trials. We might speculate that difficulties in enrolling patients, as happens in other rare diseases, may have discouraged trials\' implementation in favor of drugs already approved for MTC. However, given the concrete improvement in the comprehension of the molecular basis of PrIn effects in MTC, new clinical trials with accurate inclusion criteria of enrollment might be warranted, in order to ascertain whether this treatment, alone or in combination with other drugs, could indeed represent an option to enhance the therapeutic response, and to ultimately improve patients\' outcome and survival.