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Published on: April 22, 2019
One shoot, three birds: Targeting NEK2 orchestrates chemoradiotherapy, targeted therapy, and immunotherapy in cancer
Xing Huang1, Gang Zhang1, Tianyu Tang1
1Zhejiang 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.
Abstract:
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.
Insights
Targeting NEK2, a key kinase, offers a novel strategy for combined anti-cancer effects. This approach may enhance chemoradiotherapy, targeted therapy, and immunotherapy, potentially reducing side effects.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Combinational cancer therapy improves outcomes but increases adverse reactions.
- Targeting single proteins with multiple roles offers a strategy for combined anti-tumor effects.
- NEK2 (NIMA-related kinase 2) is a serine/threonine kinase implicated in cell cycle regulation.
Purpose of the Study:
- To review the role of NEK2 in cancer progression and therapeutic resistance.
- To highlight NEK2's emerging function in mediating tumor immune escape via PD-L1 stabilization.
- To discuss the potential of targeting NEK2 as a mono-agent strategy for combined anti-cancer effects.
Main Methods:
- Literature review of studies on NEK2 expression and function in various tumor types.
- Analysis of NEK2's role in cell cycle regulation, tumor progression, and therapeutic resistance.
- Investigation of NEK2's involvement in immune evasion mechanisms, including PD-L1 regulation.
Main Results:
- NEK2 is overexpressed across a wide range of tumors, correlating with progression and resistance.
- NEK2 promotes tumorigenesis through aberrant cell cycle control.
- NEK2 stabilizes PD-L1 expression, contributing to tumor immune escape.
Conclusions:
- NEK2 is a promising therapeutic target for cancer treatment.
- Targeting NEK2 can potentially enhance existing therapies like chemoradiotherapy, targeted therapy, and immunotherapy.
- A mono-agent strategy targeting NEK2 may achieve combined anti-cancer effects and potentially mitigate adverse reactions.
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