Research ArticleHead and Neck Cancer

Uroporphyrinogen Decarboxylase Is a Radiosensitizing Target for Head and Neck Cancer

Science Translational Medicine  26 Jan 2011:
Vol. 3, Issue 67, pp. 67ra7
DOI: 10.1126/scitranslmed.3001922

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 A Lightning UROD for Head and Neck Cancer

They say lightning never strikes the same place twice—unless, of course, that place is a lightning rod. This metal conductor draws damaging bolts to itself and away from sensitive and important structures. Cancer therapies would benefit from similar specificity. The ability to direct radiation and chemotherapy selectively toward cancer cells would decrease treatment side effects and improve patient prognosis. Ito et al. have found that uroporphyrinogen decarboxylase (UROD) can act as a lightning rod for cancer cells, sensitizing them to radiotherapy.

Head and neck cancer (HNC) comprises a diverse group of tumors of the upper respiratory and digestive tracts. Alcohol and tobacco use are strongly associated with risk for developing HNC. Using a high-throughput RNA interference screen, the authors identified UROD, an enzyme involved in heme biosynthesis, as a target for enhanced radiosensitization of these tumor types. Knockdown of UROD gene expression with a specific small inhibitory RNA molecule increased cancer cell death both in vitro and in vivo, likely through the production of reactive oxygen species and the resultant rise in oxidative stress. Moreover, elevated amounts of UROD were observed in HNC specimens, and low amounts of cancer-associated UROD correlated with improved patient survival. The sensitizing effects of UROD down-regulation extended to other cancer types and were applicable to both radiation and chemotherapy. These findings suggest that UROD represents a new target for drugs that help cell-killing agents attack tumors and spare normal cells.


  • Citation: E. Ito, S. Yue, E. H. Moriyama, A. B. Hui, I. Kim, W. Shi, N. M. Alajez, N. Bhogal, G. Li, A. Datti, A. D. Schimmer, B. C.Wilson, P. P. Liu, D. Durocher, B. G. Neel, B. O'Sullivan, B. Cummings, R. Bristow, J. Wrana, F.-F. Liu, Uroporphyrinogen Decarboxylase Is a Radiosensitizing Target for Head and Neck Cancer. Sci. Transl. Med. 3, 67ra7 (2011).