Evolutionary Action Score of TP53 Coding Variants Is Predictive of Platinum Response in Head and Neck Cancer Patients
| Autor: | Alexandra M. Ward, Marek Kimmel, Heath D. Skinner, Thomas J. Ow, Ameeta A. Patel, Thomas O. McDonald, David M. Neskey, Paolo Bossi, Teng-Kuei Hsu, Jeffrey N. Myers, Mei Zhao, Federica Perrone, Abdullah A. Osman, Panagiotis Katsonis, Adel K. El-Naggar, Marcus V. Ortega Alves, Curtis R. Pickering, Erich M. Sturgis, Stephanie C. Hicks, Merrill S. Kies, Lisa Licitra, Olivier Lichtarge, Mitchell J. Frederick |
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| Rok vydání: | 2015 |
| Předmět: |
Male
Oncology Cancer Research medicine.medical_specialty medicine.medical_treatment Gene Expression Mice Nude Antineoplastic Agents Drug resistance medicine.disease_cause Article stomatognathic system Cell Line Tumor Internal medicine medicine Carcinoma Animals Humans Neoplasm neoplasms Cisplatin Mutation Chemotherapy business.industry Head and neck cancer Middle Aged medicine.disease Xenograft Model Antitumor Assays Head and neck squamous-cell carcinoma Tongue Neoplasms Drug Resistance Neoplasm Carcinoma Squamous Cell Female Tumor Suppressor Protein p53 business medicine.drug |
| Zdroj: | Cancer Research. 75:1205-1215 |
| ISSN: | 1538-7445 0008-5472 |
| Popis: | 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. Cancer Res; 75(7); 1205–15. ©2015 AACR. |
| Databáze: | OpenAIRE |
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