Abstract:
:TP53 is the most frequently altered gene in head and neck squamous cell carcinoma (HNSCC), with mutations occurring in over two thirds of cases; however, the predictive response of these mutations to cisplatin-based therapy remains elusive. In the current study, we evaluate the ability of the Evolutionary Action score of TP53-coding variants (EAp53) to predict the impact of TP53 mutations on response to chemotherapy. The EAp53 approach clearly identifies a subset of high-risk TP53 mutations associated with decreased sensitivity to cisplatin both in vitro and in vivo in preclinical models of HNSCC. Furthermore, EAp53 can predict response to treatment and, more importantly, a survival benefit for a subset of head and neck cancer patients treated with platinum-based therapy. Prospective evaluation of this novel scoring system should enable more precise treatment selection for patients with HNSCC.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Osman AA,Neskey DM,Katsonis P,Patel AA,Ward AM,Hsu TK,Hicks SC,McDonald TO,Ow TJ,Alves MO,Pickering CR,Skinner HD,Zhao M,Sturgis EM,Kies MS,El-Naggar A,Perrone F,Licitra L,Bossi P,Kimmel M,Frederick MJ,Lichtargedoi
10.1158/0008-5472.CAN-14-2729subject
Has Abstractpub_date
2015-04-01 00:00:00pages
1205-15issue
7eissn
0008-5472issn
1538-7445pii
0008-5472.CAN-14-2729journal_volume
75pub_type
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