© The Author 2006. Published by Oxford University Press.
EDITORIAL |
Respecting Cancer Drug Transportability: A Basis for Successful Lead Selection
Correspondence to: Edward A. Sausville, MD, PhD, Marlene & Stewart Greenebaum Cancer Center, University of Maryland, 22 South Greene Street, Baltimore, MD 21201 (e-mail: esausville@umm.edu).
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Tirapazamine is a prodrug that yields a DNA-directed alkylating agent after activation in hypoxic tumor cells. The basis for its development was its selective activation in that fraction of the tumor cell population that is most refractory to radiation and conventional chemotherapeutics (1). Yet the actual level of clinical activity attributable to tirapazamine has been modest (2). Therefore, a reexamination of the basis for the drug's action is timely if this general strategy is to be further improved. Recent studies on the mechanisms allowing cancer cells to proliferate and function in a hypoxic environment have led to the conclusion that persistent activation of hypoxia-inducible factor, with the attendant downstream activation of angiogenesis and glycolytic activity, is a crucial difference in behavior of