Not so WEE: targeting G₂/M to kill mesothelioma cells

Cancer Biol Ther. 2014 Apr;15(4):351-2. doi: 10.4161/cbt.27851. Epub 2014 Feb 4.

Abstract

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).

Keywords: CDK1; G2/M checkpoint; MK-1775; WEE1; apoptosis; cisplatin; mesothelioma.

Publication types

  • Research Support, N.I.H., Extramural
  • Comment

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Cell Cycle Proteins / antagonists & inhibitors*
  • Cisplatin / pharmacology*
  • G2 Phase Cell Cycle Checkpoints*
  • Humans
  • Lung Neoplasms / drug therapy*
  • Mesothelioma / drug therapy*
  • Mesothelioma, Malignant
  • Nuclear Proteins / antagonists & inhibitors*
  • Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Pyrazoles / pharmacology*
  • Pyrimidines / pharmacology*
  • Pyrimidinones

Substances

  • Antineoplastic Agents
  • Cell Cycle Proteins
  • Nuclear Proteins
  • Pyrazoles
  • Pyrimidines
  • Pyrimidinones
  • Protein-Tyrosine Kinases
  • WEE1 protein, human
  • adavosertib
  • Cisplatin