Balaji Krishnamachary1, Louis Dore-Savard1, Santosh Kumar Bharti1, Flonne Wildes1, Yelena Mironchik1, and Zaver M Bhujwalla1
Hypoxic
environments frequently exist in solid tumors and result in resistance to
therapy and the evolution of a more lethal phenotype. Here, we have genetically engineered
human prostate cancer PC-3 cells to report on hypoxia and also express yeast
cytosine deaminase under the control of hypoxia response elements to convert
the prodrug 5-fluorocytosine to 5-Fluorouracil.
We also show that selective killing of hypoxic cells significantly
reduces tumor growth.