title: Wee1 kinase as a target for cancer therapy.
abstract: Wee1, a protein kinase, regulates the G 2 checkpoint in response to DNA damage. Preclinical studies have elucidated the role of wee1 in DNA damage repair and the stabilization of replication forks, supporting the validity of wee1 inhibition as a viable therapeutic target in cancer. MK-1775, a selective and potent small-molecule inhibitor of wee1, is under clinical development as a potentiator of DNA damage caused by cytotoxic chemotherapies. We present a review of the role of wee1 in the cell cycle and DNA replication and summarize the clinical development to date of this novel class of anticancer agents.
authors.affiliation: Center for Cancer Research; National Cancer Institute; Bethesda, MD USA.
authors.forename: Khanh
authors.initials: K
authors.lastname: Do
authors.forename: James H
authors.initials: JH
authors.lastname: Doroshow
authors.forename: Shivaani
authors.initials: S
authors.lastname: Kummar
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use / Q000633:toxicity; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002986:Clinical Trials as Topic; D004249:DNA Damage / Q000187:drug effects / Q000528:radiation effects; D004260:DNA Repair; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy*; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011720:Pyrazoles / Q000627:therapeutic use / Q000633:toxicity; D011743:Pyrimidines / Q000627:therapeutic use / Q000633:toxicity; D011744:Pyrimidinones; D034622:RNA Interference
chemical_list: D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; D011720:Pyrazoles; D011743:Pyrimidines; D011744:Pyrimidinones; D011505:Protein-Tyrosine Kinases; C499349:WEE1 protein, human; C549567:adavosertib
keywords: DNA damage; G2 checkpoint; MK 1775; cell cycle; cyclin-dependent kinase