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Reactive oxygen species-mediated therapeutic control of bladder cancer

Nature Reviews Urology volume 8, pages 608–616 (2011)Cite this article

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Abstract

Urinary bladder cancer is the fifth most common cancer in the US and the most costly cancer to manage because it requires life-long surveillance to monitor for recurrence and advanced progression. Urothelial carcinomas account for more than 90% of urinary bladder cancer cases. Transurethral resection and intravesical chemotherapy or immunotherapy are effective short-term treatments of urothelial carcinoma, but long-term management has not yet been optimized. Recent therapeutic strategies emphasize the targeted interference with aberrantly-regulated signaling modulators that result from genomic alterations. However, targeted therapeutic agents might not distinguish cancer cells from their normal counterparts, resulting in undesirable adverse effects. Thus, a new approach for the treatment of urothelial carcinoma has been suggested that differentially augments cancer-associated events, leading to selective death of cancer cells but not normal cells. Many aberrantly-regulated signaling modulators are associated with the elevation of reactive oxygen species (ROS), and an increasing number of studies report agents with the ability to induce ROS in cancer cells. Accordingly, therapeutic augmentation of ROS to a lethal level in cancer cells only would induce selective death of tumor cells but not normal cells, leading to a highly effective chemotherapy strategy for urothelial carcinoma.

Key Points

  • Human urinary bladder cancer is the fifth most common cancer in the US and the most costly cancer to manage owing to high rates of recurrence and progression

  • Urothelial papillary carcinoma, carcinoma in situ, and invasive carcinoma of the bladder account for more than 90% of urinary bladder cancer cases

  • Genomic alterations of oncogenes and tumor suppressor genes are identified by their tight association with the development and progression of urothelial carcinomas

  • Many aberrantly-regulated signaling modulators, resulting from genomic alterations, detectably potentiate the reactive oxygen species (ROS)-generating machinery in urothelial carcinoma cells

  • An increasing number of studies report therapeutic agents that induce ROS elevation in cancer cells

  • A ROS-mediated therapeutic strategy that augments cancer-associated ROS elevation could selectively induce apoptosis of urothelial carcinoma cells, bypassing normal cells and producing minimal adverse effects

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Figure 1: Divergent pathways of the genomic alterations involved in urothelial tumorigenesis.
Figure 2: Genetic alteration-potentiated ROS machinery for selective cell death.

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  1. Anticancer Molecular Oncology Laboratory, College of Veterinary Medicine, The University of Tennessee, 2407 River Drive, Knoxville, 37996, TN, USA

    Hwa-Chain R. Wang & Shambhunath Choudhary

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H.-C. R. Wang and S. Choudhary contributed equally to researching data, discussing content and reviewing this manuscript. H.-C. R. Wang wrote the majority of the paper, with contributions from S. Choudhary.

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Wang, HC., Choudhary, S. Reactive oxygen species-mediated therapeutic control of bladder cancer. Nat Rev Urol 8, 608–616 (2011). https://doi.org/10.1038/nrurol.2011.135

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  • DOI: https://doi.org/10.1038/nrurol.2011.135

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