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Molecular Medicine

, Volume 18, Issue 2, pp 244–249 | Cite as

Constitutive Overexpression of the Oncogene Racl in the Airway of Recurrent Respiratory Papillomatosis Patients Is a Targetable Host-Susceptibility Factor

  • Alexandra V. Lucs
  • Rong Wu
  • Virginia Mullooly
  • Allan L. Abramson
  • Bettie M. Steinberg
Research Article

Abstract

Recurrent respiratory papillomatosis (RRP) is caused by human papillomaviruses (HPVs), primarily types 6 and 11. The disease is characterized by multiple recurrences of airway papillomas, resulting in high levels of morbidity and significant mortality. The prevalence of latent HPV in the larynx of the general population is much greater than the prevalence of RRP, suggesting a host-susceptibility factor for disease. We report that the oncogene Rac1 and its downstream product cyclooxygenase-2 (COX-2) are both constitutively expressed at high levels throughout the airway of these patients, independent of active HPV infection. Use of the COX-2 inhibitor celecoxib in primary papilloma cell culture resulted in the downregulation of HPV transcription. Furthermore, a proof-of-principle study treating three patients with severe RRP with celecoxib resulted in remission of disease in all cases. Therefore, we have identified the first pharmacologically targetable host-susceptibility pathway that contributes to RRP recurrence.

Notes

Acknowledgments

We gratefully acknowledge Marc Symons for helpful suggestions and critical reading of the manuscript. This work was supported by grants 5R01DC00203, 5R01DC008579, 1R01DC008579-S1 and 1F32DC011446 from the National Institute on Deafness and Other Communication Disorders.

The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute on Deafness and Other Communication Disorders or the National Institutes of Health. Celecoxib and matching placebo were provided by grant 2004-0029 (WS287683) from Pfizer Global Pharmaceuticals, New York, New York, USA.

Celecoxib was used for the clinical study and was obtained through a grant from Pfizer.

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Authors and Affiliations

  • Alexandra V. Lucs
    • 1
  • Rong Wu
    • 1
    • 2
  • Virginia Mullooly
    • 2
  • Allan L. Abramson
    • 1
    • 2
    • 3
  • Bettie M. Steinberg
    • 1
    • 2
    • 3
  1. 1.Feinstein Institute for Medical ResearchNorth Shore-Long Island Jewish (LIJ) Health SystemManhassetUSA
  2. 2.Department of Otolaryngology and Communicative DisordersLong Island Jewish Medical CenterNew Hyde ParkUSA
  3. 3.Hofstra North Shore-LIJ School of MedicineManhassetUSA

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