Not so WEE: targeting G₂/M to kill mesothelioma cells.
It has been known for many years that manipulation of cell cycle checkpoint function represents one approach by which the toxicity of chemotherapy and of ionizing radiation can be increased in tumor cells. (1)(-) (3) In particular, abrogation of the G 2/M checkpoint has been shown to enhance the lethality of a wide range of toxic stresses. (1)(-) (3) Inhibition of the G 2/M checkpoint after chemotherapy/irradiation would result in tumor cells entering mitosis with damaged DNA, which would in turn result in loss of clonogenic survival (i.e., a lethal mitosis).
Department of Biochemistry and Molecular Biology; Massey Cancer Center; Virginia Commonwealth University; Richmond, VA USA.
Paul
P
Dent
D000970:Antineoplastic Agents / Q000494:pharmacology*; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors*; D002945:Cisplatin / Q000494:pharmacology*; D059565:G2 Phase Cell Cycle Checkpoints; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008654:Mesothelioma / Q000188:drug therapy*; D000086002:Mesothelioma, Malignant; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011720:Pyrazoles / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D011744:Pyrimidinones
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; D002945:Cisplatin
CDK1; G2/M checkpoint; MK-1775; WEE1; apoptosis; cisplatin; mesothelioma