In a study reported in Clinical Cancer Research, Moser and colleagues used RNA interference kinase viability screens to identify survival kinases (involved in G2-M cell-cycle checkpoint, SFK, PI3K, and FAK pathways) in p53-mutant head and neck squamous cell carcinoma. Selected kinase targets were tested against a panel of kinase inhibitors.
Study of the WEE1 kinase showed that both RNA interference-mediated knockdown and a specific kinase inhibitor (MK-1775) produced significant inhibition of cell viability and apoptosis. Sensitivity to the WEE1 kinase inhibitor was determined in part by p53 mutational status and was due to unscheduled mitotic entry. The inhibitor was active as a single agent and potentiated the activity of cisplatin in a p53-mutant head and neck squamous cell carcinoma xenograft model.
The investigators concluded: “WEE1 kinase is a potential therapeutic drug target for [head and neck squamous cell carcinoma]. This study supports the application of a functional kinomics strategy to identify novel therapeutic targets for cancer.” ■
Moser R, et al: Clin Cancer Res 20:4274-4288, 2014.