Targeting protein kinase CK2 in the treatment of cholangiocarcinoma.
Targeting protein kinase CK2 in the treatment of cholangiocarcinoma.
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DOI：
10.37349/etat.2021.00055
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发表时间：
2021
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胆管癌（CCA）是一种预后极差且治疗选择有限的疾病。尽管针对 CCA 中发现的特定突变的靶向治疗正在变得可行，并且显示出巨大的潜力，但许多肿瘤不携带可操作的突变，而在那些携带可操作突变的肿瘤中，出现耐药性可能是治疗的结果。针对在 CCA 细胞中表现出较高活性但不会因突变而改变的酶和其他蛋白质的治疗靶向是治疗靶标阴性和耐药疾病的潜在策略。蛋白激酶 CK2 (CK2) 是一种普遍表达的激酶，在包括 CCA 在内的多种癌症类型中表达增加且活性增加。几种有效的 CK2 抑制剂正处于临床前开发阶段或在各种临床试验中进行评估，通常与诱导 DNA 损伤的药物联合使用。本综述概述了 CK2 在 CCA 中的重要性，并评估了在评估 CK2 抑制作为该疾病的治疗策略方面所取得的进展。根据CK2蛋白的表达水平或活性和/或与诱导DNA损伤或抑制细胞周期进展的药物相结合来靶向CK2，对于缺乏可操作突变的肿瘤或对靶向治疗产生耐药性的肿瘤来说可能是一个可行的选择。
Cholangiocarcinoma (CCA) is a disease with a very poor prognosis and limited treatment options. Although targeted therapies directed towards specific mutations found in CCA are becoming available and are showing great potential, many tumors do not carry actionable mutations and, in those that do, the emergence of drug resistance is a likely consequence of treatment. Therapeutic targeting of enzymes and other proteins that show elevated activity in CCA cells but which are not altered by mutation is a potential strategy for the treatment of target negative and drug-resistant disease. Protein kinase CK2 (CK2) is a ubiquitously expressed kinase that has increased expression and increased activity in a variety of cancer types including CCA. Several potent CK2 inhibitors are in pre-clinical development or under assessment in a variety of clinical trials often in combination with drugs that induce DNA damage. This review outlines the importance of CK2 in CCA and assesses the progress that has been made in the evaluation of CK2 inhibition as a treatment strategy in this disease. Targeting CK2 based on the expression levels or activity of this protein and/or in combination with drugs that induce DNA damage or inhibit cell cycle progression, could be a viable option for tumors that lack actionable mutations, or for tumors that develop resistance to targeted treatments.