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Targeting WEE1: a rising therapeutic strategy for hematologic malignancies

LI Hao-Bo¹, Thekra Khushafa¹, YANG Chao-Ying¹, ZHU Li-Ming², SUN Xing¹, NIE Ling³, LIU Jing^1,*

¹Department of Hematology, The Second Xiangya Hospital, Molecular Biology Research Center, School of Life Sciences, Hunan Province Key Laboratory of Basic and Applied Hematology, Central South University, Changsha 410083, China；²Department of Respiratory and Critical Care Medicine, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), China Clinical Medicine Research Center for Respiratory Rehabilitation in Hunan Province, Changsha 410005, China；³Department of Hematology, Xiangya Hospital, Central South University, Changsha 410008, China

Abstract

Hematologic malignancies, including leukemia, lymphoma, and multiple myeloma, are hazardous diseases characterized by the uncontrolled proliferation of cancer cells. Dysregulated cell cycle resulting from genetic and epigenetic abnormalities constitutes one of the central events. Importantly, cyclin-dependent kinases (CDKs), complexed with their functional partner cyclins, play dominating roles in cell cycle control. Yet, efforts in translating CDK inhibitors into clinical benefits have demonstrated disappointing outcomes. Recently, mounting evidence highlights the emerging significance of WEE1 G2 checkpoint kinase (WEE1) to modulate CDK activity, and correspondingly, a variety of therapeutic inhibitors have been developed to achieve clinical benefits. Thus, WEE1 may become a promising target to modulate the abnormal cell cycle. However, its function in hematologic diseases remains poorly elucidated. In this review, focusing on hematologic malignancies, we describe the biological structure of WEE1, emphasize the latest reported function of WEE1 in the carcinogenesis, progression, as well as prognosis, and finally summarize the therapeutic strategies by targeting WEE1.

Key words: hematologic malignancies; cell cycle; cyclin-dependent kinases (CDKs); WEE1

Received: 　　Accepted:

Corresponding author: 刘静　　E-mail:

DOI: 10.13294/j.aps.2025.0058

Citing This Article：

LI Hao-Bo, Thekra Khushafa, YANG Chao-Ying, ZHU Li-Ming, SUN Xing, NIE Ling, LIU Jing. Targeting WEE1: a rising therapeutic strategy for hematologic malignancies. Acta Physiol Sin 2025; 77 (5): 839-854