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

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 t...

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Bibliographic Details
Published in:Molecular medicine (Cambridge, Mass.) Mass.), 2012-02, Vol.18 (2), p.244-249
Main Authors: Lucs, Alexandra V., Wu, Rong, Mullooly, Virginia, Abramson, Allan L., Steinberg, Bettie M.
Format: Article
Language:English
Subjects:
Apoptosis
Biopsy
Clinical trials
Epidermal growth factor
Human papillomavirus
Infections
Patients
Proteins
Signal transduction
Statistical analysis
Surgery
Tumors
Viral infections
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Summary: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.
ISSN:1076-1551
1528-3658
DOI:10.2119/molmed.2011.00447