Abstract
Mutations in TP53, encoding the master tumor suppressor p53, have posed a developmental therapeutic dilemma due to inability to target loss of function. Inhibition of WEE1 or CHK1 kinase, negative regulators of the G2-M checkpoint, selectively sensitizes p53-deficient cells to exogenous DNA damage, abrogating G2 arrest and precipitating mitotic catastrophe.
©2014 American Association for Cancer Research.
Publication types
-
Research Support, N.I.H., Extramural
-
Comment
MeSH terms
-
Animals
-
Carcinoma, Squamous Cell / metabolism*
-
Cell Cycle Proteins / antagonists & inhibitors*
-
Head and Neck Neoplasms / metabolism*
-
Humans
-
Nuclear Proteins / antagonists & inhibitors*
-
Protein Kinase Inhibitors / pharmacology*
-
Protein Kinases / chemistry*
-
Protein-Tyrosine Kinases / antagonists & inhibitors*
-
RNA, Small Interfering / genetics*
-
Tumor Suppressor Protein p53 / metabolism*
Substances
-
Cell Cycle Proteins
-
Nuclear Proteins
-
Protein Kinase Inhibitors
-
RNA, Small Interfering
-
Tumor Suppressor Protein p53
-
Protein Kinases
-
Protein-Tyrosine Kinases