Use of reprogrammed cells to identify therapy for respiratory papillomatosis

N Engl J Med. 2012 Sep 27;367(13):1220-7. doi: 10.1056/NEJMoa1203055.

Abstract

A patient with a 20-year history of recurrent respiratory papillomatosis had progressive, bilateral tumor invasion of the lung parenchyma. We used conditional reprogramming to generate cell cultures from the patient's normal and tumorous lung tissue. Analysis revealed that the laryngeal tumor cells contained a wild-type 7.9-kb human papillomavirus virus type 11 (HPV-11) genome, whereas the pulmonary tumor cells contained a 10.4-kb genome. The increased size of the latter viral genome was due to duplication of the promoter and oncogene regions. Chemosensitivity testing identified vorinostat as a potential therapeutic agent. At 3 months after treatment initiation, tumor sizes had stabilized, with durable effects at 15 months.

Publication types

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

MeSH terms

  • Antineoplastic Agents / therapeutic use*
  • Cells, Cultured
  • DNA, Viral / isolation & purification
  • Gene Expression
  • Genome, Viral
  • Human papillomavirus 11 / genetics
  • Humans
  • Hydroxamic Acids / therapeutic use*
  • Laryngeal Neoplasms / surgery
  • Laryngeal Neoplasms / virology
  • Lung / cytology*
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / pathology*
  • Lung Neoplasms / virology
  • Male
  • Mutation
  • Papillomavirus Infections / complications
  • Papillomavirus Infections / drug therapy*
  • Papillomavirus Infections / pathology
  • Papillomavirus Infections / surgery
  • RNA, Messenger / metabolism
  • RNA, Viral / analysis
  • Respiratory Tract Infections / complications
  • Respiratory Tract Infections / drug therapy*
  • Respiratory Tract Infections / pathology
  • Respiratory Tract Infections / surgery
  • Tumor Cells, Cultured
  • Vorinostat
  • Young Adult

Substances

  • Antineoplastic Agents
  • DNA, Viral
  • Hydroxamic Acids
  • RNA, Messenger
  • RNA, Viral
  • Vorinostat

Supplementary concepts

  • Recurrent respiratory papillomatosis