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 epige...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.展开更多
基金supported by grants from the National Natural Science Foundation of China(No.81920108004,82270127,82203880)the Hunan Provincial Natural Science Foundation of China(No.2023JJ30928,2024JJ3037)+2 种基金the Changsha Municipal Natural Sci-Science Foundation(No.kq2208382)the Fellowship of the China Postdoctoral Science Foundation(No.2023T160740)the Hunan Province Clinical Medical Technology Innovation Guidance Project(No.2021SK50917,2023SK4056)。
文摘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.
