CHK It Out! Blocking WEE Kinase Routs TP53 Mutant Cancer
نویسندگان
چکیده
منابع مشابه
CHK it out! Blocking WEE kinase routs TP53 mutant cancer.
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.
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Although cisplatin has played a role in "standard-of-care" multimodality therapy for patients with advanced squamous cell carcinoma of the head and neck (HNSCC), the rate of treatment failure remains particularly high for patients receiving cisplatin whose tumors have mutations in the TP53 gene. We found that cisplatin treatment of HNSCC cells with mutant TP53 leads to arrest of cells in the G2...
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متن کاملCancer Therapeutics Insights Chk1/2 Inhibition Overcomes the Cisplatin Resistance of Head and Neck Cancer Cells Secondary to the Loss of Functional p53
Despite the use ofmultimodality therapy using cisplatin to treat patientswith advanced stage squamous cell carcinoma of the head and neck (HNSCC), there is an unacceptably high rate of treatment failure. TP53 is the most commonlymutated gene inHNSCC, and the impact of p53mutation on response to cisplatin treatment is poorly understood. Here, we show unambiguously that wild-type TP53 (wtp53) is ...
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ژورنال
عنوان ژورنال: Clinical Cancer Research
سال: 2014
ISSN: 1078-0432,1557-3265
DOI: 10.1158/1078-0432.ccr-14-0720