Laboratoire d'Immunologie et Immunothérapie des Cancers, EPHE, PSL Research University, 75000 Paris, France; LIIC, EA7269, Université de Bourgogne Franche-Comté, 21000 Dijon, France.
Laboratoire d'Immunologie et Immunothérapie des Cancers, EPHE, PSL Research University, 75000 Paris, France; LIIC, EA7269, Université de Bourgogne Franche-Comté, 21000 Dijon, France.
Biochem Pharmacol. 2020 Jun;176:113855. doi: 10.1016/j.bcp.2020.113855. Epub 2020 Feb 13.
The deregulation of a wide variety of protein kinases is associated with cancer cell initiation and tumor progression. Owing to their indispensable function in signaling pathways driving malignant cell features, protein kinases constitute major therapeutic targets in cancer. Over the past two decades, intense efforts in drug development have been dedicated to this field. The development of protein kinase inhibitors (PKIs) have been a real breakthrough in targeted cancer therapy. Despite obvious successes across patients with different types of cancer, the development of PKI resistance still prevails. Combination therapies are part of a comprehensive approach to address the problem of drug resistance. The therapeutic use of nitric oxide (NO) donors to bypass PKI resistance in cancer has never been tested in clinic yet but several arguments suggest that the combination of PKIs and NO donors may exert a potential anticancer effect. The present review summarized the current state of knowledge on common targets to both PKIs and NO. Herein, we attempt to provide the rationale underlying a potential combination of PKIs and NO donors for future directions and design of new combination therapies in cancer.
蛋白激酶的广泛失调与癌细胞的起始和肿瘤的进展有关。由于它们在驱动恶性细胞特征的信号通路中不可或缺的功能，蛋白激酶成为癌症治疗的主要靶点。在过去的二十年中，药物开发领域投入了巨大的努力。蛋白激酶抑制剂（PKIs）的发展是靶向癌症治疗的真正突破。尽管不同类型癌症的患者都取得了明显的成功，但 PKI 耐药性的发展仍然存在。联合治疗是解决耐药性问题的综合方法的一部分。一氧化氮（NO）供体在癌症中用于绕过 PKI 耐药性的治疗用途尚未在临床上进行测试，但有几个论点表明，PKIs 和 NO 供体的联合可能发挥潜在的抗癌作用。本综述总结了目前关于 PKIs 和 NO 共同靶点的知识现状。在此，我们试图为 PKI 和 NO 供体的潜在联合提供一个潜在的组合的基础，以用于癌症的新联合治疗的未来方向和设计。
