title: Constitutive overexpression of the oncogene Rac1 in the airway of recurrent respiratory papillomatosis patients is a targetable host-susceptibility factor.
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.
authors: Feinstein Institute for Medical Research, North Shore-Long Island Jewish-LIJ Health System, Manhasset, New York, United States of America.
authors: Alexandra V
authors: AV
authors: Lucs
authors: Rong
authors: R
authors: Wu
authors: Virginia
authors: V
authors: Mullooly
authors: Allan L
authors: AL
authors: Abramson
authors: Bettie M
authors: BM
authors: Steinberg
mesh_terms: D000328:Adult; D000068579:Celecoxib; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D052140:Human papillomavirus 11; D052162:Human papillomavirus 16; D006801:Humans; D008297:Male; D030361:Papillomavirus Infections / Q000188:drug therapy / Q000378:metabolism*; D011720:Pyrazoles / Q000494:pharmacology / Q000627:therapeutic use; D012141:Respiratory Tract Infections / Q000188:drug therapy / Q000378:metabolism*; D013449:Sulfonamides / Q000494:pharmacology / Q000627:therapeutic use; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D011720:Pyrazoles; C107953:RAC1 protein, human; D013449:Sulfonamides; D051546:Cyclooxygenase 2; D020830:rac1 GTP-Binding Protein; D000068579:Celecoxib