p16(INK4A) adenovirus-mediated gene therapy for human head and neck squamous cell cancer

James W. Rocco, Daqing Li, William H. Liggett, Ling Duan, John K. Saunders, David Sidransky, Bert W. O'Malley

Research output: Contribution to journalArticle

Abstract

Inactivation of the tumor suppressor gene p16(INK4A) is the most common genetic alteration in human head and neck squamous cell cancer (HNSCC), making it an ideal target for gene replacement. We constructed a replication- defective, recombinant adenovirus capable of directing a high level of p16(INK4A) protein expression (Ad5-p16) to investigate its benefit in treating HNSCC. Initial in vitro experiments in four human HNSCC cell lines demonstrated that Ad5-p16 treatment significantly inhibits cell growth with up to 96% efficiency. Flow cytometric analysis showed that Ad5-p16 induced a maximum G1-S cell cycle arrest of 90%. Subsequent studies in a nude mouse model demonstrated that Ad5-p16 treatment significantly reduced (cell line 011) or stabilized (cell line 012) established tumors when compared with control treatments (P < 0.008). These results demonstrate for the first time a significant antitumor effect of Ad5-p16 against human HNSCC in vivo and support the potential application of Ad5-p16 to treat locally advanced, unresectable, or metastatic head and neck cancer, as well as microscopic residual disease after surgical resection.

Original languageEnglish (US)
Pages (from-to)1697-1704
Number of pages8
JournalClinical Cancer Research
Volume4
Issue number7
StatePublished - Jul 1 1998

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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  • Cite this

    Rocco, J. W., Li, D., Liggett, W. H., Duan, L., Saunders, J. K., Sidransky, D., & O'Malley, B. W. (1998). p16(INK4A) adenovirus-mediated gene therapy for human head and neck squamous cell cancer. Clinical Cancer Research, 4(7), 1697-1704.