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Hypoxic Tumors and Cancer Treatment - Page 2

© David Olle

Hypoxic-cell selective agents

Hypoxic cytotoxins are drugs that are specifically designed to be active in the hypoxic cell. Their action is complimentary to radiation and chemotherapy, but their effect is not dependent upon the use of the other therapies. A current strategy is to use a combination of treatments in order to kill all cells in the tumor. The hypoxic cytotoxins kill the more hypoxic cells in the interior of the tumor, while the conventional chemotherapeutic drugs act on cells nearer to the capillary. Mitomycin C was the first drug in this category to be tested. Although mitomycin C has been shown to be beneficial, its use appears to be limited, since it can be used only twice during radiotherapy. Tirapazamine appears to be a particularly promising drug, as it kills cells at low concentrations, and has a much greater differential toxicity to hypoxic cells than other known drugs. In order to become active in the cell, tirapazamine must be converted into a reactive radical by a reductase enzyme. The radical then causes breaks in the DNA molecule. In the non-hypoxic cell, oxygen removes an electron from the radical, returning the compound to the inactive drug. Tirapazamine is currently being studied in clinical studies in combination with the chemotherapeutic drug, cisplatin. Porfiromycin is another promising drug that shows a more preferential toxicity towards hypoxic cells compared with mitomycin C.

References

1.Brown, M. The hypoxic cell. Cancer Research, Vol. 59, pp. 5863-5870 (Dec. 1, 1999).

2. Keyes, S. et. al. Porfiromycin as a bioreductive alkylating agent with selective toxicity to hypoxic EMT6 tumor cells in vivo and in vitro.Cancer Research, Vol. 45, No. 8, pp. 3642-3645 (1985).

3. Harrison, L. Impact of tumor hypoxia and anemia on radiation therapy outcomes. The Oncologist, Vol.7, No. 6, pp.492-508 (Dec. 2002).

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