Digestive-system cancers represent major threats to human health;however,the mechanisms underlying tumorigenesis and radiochemotherapy resistance have remained elusive.Therefore,an urgent need exists for identifying k...Digestive-system cancers represent major threats to human health;however,the mechanisms underlying tumorigenesis and radiochemotherapy resistance have remained elusive.Therefore,an urgent need exists for identifying key drivers of digestive system tumorigenesis and novel targeted therapeutics.The checkpoint kinase 2(Chk2)regulates cell-cycle progression,and Chk2 dysregulation or Chk2 mutations can lead to the development of various cancers,which makes Chk2 an important research topic.This review summarizes the roles of Chk2 in DNA-damage responses,cell-cycle regulation,autophagy,and homeostasis maintenance.We describe relationships between tumorigenesis and cell-cycle dysregulation induced by Chk2 mutations.In addition,we summarize evidence indicating that Chk2 can serve as a novel therapeutic target,based on its contributions to radiochemotherapy-resistance reversion and progress made in developing antitumor agents against Chk2.The prevailing evidence supports the conclusion that further research on Chk2 will provide a deeper understanding of digestive-system tumorigenesis and should suggest novel therapeutic targets.展开更多
基金supported by the National Natural Science Foundation of China(No.82100700 to F.Y.)the China Postdoctoral Science Foundation(No.2020M670101ZX to F.Y.)+1 种基金the Fundamental Scientific Research Project from the Educational Department of Liaoning Province,China(No.LJKMZ20221191 to F.Y.)the 345 Talent Project of Shengjing Hospital of China Medical University(No.52-30B to F.Y.).
文摘Digestive-system cancers represent major threats to human health;however,the mechanisms underlying tumorigenesis and radiochemotherapy resistance have remained elusive.Therefore,an urgent need exists for identifying key drivers of digestive system tumorigenesis and novel targeted therapeutics.The checkpoint kinase 2(Chk2)regulates cell-cycle progression,and Chk2 dysregulation or Chk2 mutations can lead to the development of various cancers,which makes Chk2 an important research topic.This review summarizes the roles of Chk2 in DNA-damage responses,cell-cycle regulation,autophagy,and homeostasis maintenance.We describe relationships between tumorigenesis and cell-cycle dysregulation induced by Chk2 mutations.In addition,we summarize evidence indicating that Chk2 can serve as a novel therapeutic target,based on its contributions to radiochemotherapy-resistance reversion and progress made in developing antitumor agents against Chk2.The prevailing evidence supports the conclusion that further research on Chk2 will provide a deeper understanding of digestive-system tumorigenesis and should suggest novel therapeutic targets.
