The tumor suppressor p53 is mutated in over 50% of head and neck squamous cell carcinomas (HNSCC), yet there are currently no available therapies to target it. CTD2 researchers at the Fred Hutchison Cancer Research Center hypothesized that HNSCC cancer cells with p53 mutations are dependent on particular kinases for survival. In a study published in Clinical Cancer Research, they sought to identify these kinases using RNAi against known kinase genes in mouse and human cell lines. The screen revealed several potential therapeutic targets, including WEE1, CHK1, AURKA and NEK4.
The authors focused preclinical validation experiments on WEE1, a kinase that regulates G2/M cell cycle transition. Cisplatin is the standard chemotherapy used to treat HNSCCs, so they studied the effect of treating HNSCC xenografts with a combination of cisplatin and WEE1 inhibitor MK-1775. The combination treatment reduced xenograft tumor volume by more than 80%, about 20% more than cisplatin alone. Future studies are necessary to determine if WEE1 or other G2/M checkpoint inhibitors will be successful in treating HNSCC in the clinic.