Evolutionary Action Score of TP53 Coding Variants Is Predictive of Platinum Response in Head and Neck Cancer Patients.

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.

• Authors: Abdullah A Osman, David M Neskey, Panagiotis Katsonis, Ameeta A Patel, Alexandra M Ward, Teng-Kuei Hsu, Stephanie C Hicks, Thomas O McDonald, Thomas J Ow, Marcus Ortega Alves, Curtis R Pickering, Heath D Skinner, Mei Zhao, Eric M Sturgis, Merrill S Kies, Adel El-Naggar, Federica Perrone, Lisa Licitra, Paolo Bossi, Marek Kimmel, Mitchell J Frederick, Olivier Lichtarge, Jeffrey N Myers
• Journal: Cancer research (Cancer Res) Vol. 75 Issue 7 Pg. 1205-15 (Apr 01 2015) ISSN: 1538-7445 [Electronic] United States
• PMID: 25691460 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: ©2015 American Association for Cancer Research.

Chemical References

• Antineoplastic Agents
• TP53 protein, human
• Tumor Suppressor Protein p53
• Cisplatin

Topics

• Animals
• Antineoplastic Agents (pharmacology)
• Carcinoma, Squamous Cell (drug therapy, genetics)
• Cell Line, Tumor
• Cisplatin (pharmacology)
• Drug Resistance, Neoplasm
• Female
• Gene Expression
• Humans
• Male
• Mice, Nude
• Middle Aged
• Mutation
• Tongue Neoplasms (drug therapy, genetics)
• Tumor Suppressor Protein p53 (genetics)
• Xenograft Model Antitumor Assays