One shoot, three birds: Targeting NEK2 orchestrates chemoradiotherapy, targeted therapy, and immunotherapy in cancer treatment

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.