Cellular Oncology ( IF 6.6 ) Pub Date : 2020-10-14 , DOI: 10.1007/s13402-020-00566-w Claudio D'Amore 1 , Christian Borgo 1 , Stefania Sarno 1 , Mauro Salvi 1
Background
Protein kinase CK2 inhibition has long been considered as an attractive anti-cancer strategy based on the following considerations: CK2 is a pro-survival kinase, it is frequently over-expressed in human tumours and its over-expression correlates with a worse prognosis. Preclinical evidence strongly supports the feasibility of this target and, although dozens of CK2 inhibitors have been described in the literature so far, CX-4945 (silmitasertib) was the first that entered into clinical trials for the treatment of both human haematological and solid tumours. However, kinase inhibitor monotherapies turned out to be effective only in a limited number of malignancies, probably due to the multifaceted causes that underlie them, supporting the emerging view that multi-targeted approaches to treat human tumours could be more effective.
Conclusions
In this review, we will address combined anti-cancer therapeutic strategies described so far which involve the use of CX-4945. Data from preclinical studies clearly show the ability of CX-4945 to synergistically cooperate with different classes of anti-neoplastic agents, thereby contributing to an orchestrated anti-tumour action against multiple targets. Overall, these promising outcomes support the translation of CX-4945 combined therapies into clinical anti-cancer applications.
中文翻译:
![](https://static.x-mol.com/jcss/images/paperTranslation.png)
CK2 抑制剂 CX-4945 在抗癌联合治疗中的作用——潜在的临床相关性
背景
基于以下考虑,蛋白激酶 CK2 抑制长期以来一直被认为是一种有吸引力的抗癌策略:CK2 是一种促生存激酶,它经常在人类肿瘤中过度表达,其过度表达与更差的预后相关。临床前证据强烈支持这一目标的可行性,尽管迄今为止在文献中描述了数十种 CK2 抑制剂,但 CX-4945 (silmitasertib) 是第一个进入临床试验以治疗人类血液肿瘤和实体瘤的药物。然而,激酶抑制剂单一疗法仅对有限数量的恶性肿瘤有效,这可能是由于它们背后的多方面原因,支持了一种新兴观点,即治疗人类肿瘤的多靶点方法可能更有效。
结论
在这篇综述中,我们将讨论迄今为止描述的涉及使用 CX-4945 的联合抗癌治疗策略。来自临床前研究的数据清楚地表明 CX-4945 与不同类别的抗肿瘤药物协同合作的能力,从而有助于针对多个目标的协调抗肿瘤作用。总体而言,这些有希望的结果支持将 CX-4945 联合疗法转化为临床抗癌应用。