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

Cancer Res. 2015 Apr 1;75(7):1205-15. doi: 10.1158/0008-5472.CAN-14-2729. Epub 2015 Feb 17.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

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


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