Huang Xing, Zhang Gang, Tang Tianyu, Gao Xiang, Liang Tingbo
Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang, China; Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang, China; Zhejiang Clinical Research Center of Hepatobiliary and Pancreatic Diseases, Hangzhou 310003, Zhejiang, China; The Innovation Center for the Study of Pancreatic Diseases of Zhejiang Province, Hangzhou 310009, Zhejiang, China; Cancer Center, Zhejiang University, Hangzhou 310058, Zhejiang, China.
Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang, China; Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang, China; Zhejiang Clinical Research Center of Hepatobiliary and Pancreatic Diseases, Hangzhou 310003, Zhejiang, China; The Innovation Center for the Study of Pancreatic Diseases of Zhejiang Province, Hangzhou 310009, Zhejiang, China; Cancer Center, Zhejiang University, Hangzhou 310058, Zhejiang, China.
Biochim Biophys Acta Rev Cancer. 2022 Mar;1877(2):188696. doi: 10.1016/j.bbcan.2022.188696. Epub 2022 Feb 12.
Combinational therapy has improved the cancer therapeutic landscape but is associated with a concomitant increase in adverse side reactions. Emerging evidence proposes that targeting one core target with multiple critical roles in tumors can achieve combined anti-tumor effects. This review focuses on NEK2, a member of serine/threonine kinases, with broad sequence identity to the mitotic regulator NIMA of the filamentous fungus Aspergillus nidulans. Elevated expression of NEK2 was initially found to promote tumorigeneses through abnormal regulation of the cell cycle. Subsequent studies report that NEK2 is overexpressed in a broad spectrum of tumor types and is associated with tumor progression and therapeutic resistance. Intriguingly, NEK2 has recently been revealed to mediate tumor immune escape by stabilizing the expression of PD-L1. Targeting NEK2 is thus becoming a promising approach for cancer treatment by orchestrating chemoradiotherapy, targeted therapy, and immunotherapy. It represents a novel strategy for inducing combined anti-cancer effects using a mono-agent.
联合疗法改善了癌症治疗格局，但同时也伴随着不良反应的增加。新出现的证据表明，针对肿瘤中具有多种关键作用的一个核心靶点可以实现联合抗肿瘤效果。本综述聚焦于NEK2，它是丝氨酸/苏氨酸激酶家族的一员，与丝状真菌构巢曲霉的有丝分裂调节因子NIMA具有广泛的序列同源性。最初发现NEK2表达升高通过异常调节细胞周期促进肿瘤发生。随后的研究报告称，NEK2在多种肿瘤类型中过表达，并与肿瘤进展和治疗耐药性相关。有趣的是，最近发现NEK2通过稳定PD-L1的表达介导肿瘤免疫逃逸。因此，靶向NEK2正成为一种有前景的癌症治疗方法，可通过协调放化疗、靶向治疗和免疫治疗来实现。它代表了一种使用单一药物诱导联合抗癌效果的新策略。
