期刊
CANCER RESEARCH
卷 75, 期 7, 页码 1205-1215出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-14-2729
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资金
- University of Texas MD Anderson Cancer Center PANTHEON
- NIH [P50CA097007, C168485, 5 R90 DK071505]
- NIH/NIDCR [R01 DE14613, R01 DE024601]
- Cancer Prevention and Research Institute of Texas (CPRIT) [RP120258]
- National Research Science Award Institutional Research Training [T32GA60374]
- Cancer Center Support [GM066099]
- NSF [CCF 0905536, DBI 0851393]
- Direct For Biological Sciences
- Div Of Biological Infrastructure [1356569] Funding Source: National Science Foundation
- Div Of Biological Infrastructure
- Direct For Biological Sciences [1062455] Funding Source: National Science Foundation
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.
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