pH and drug resistance in tumors

Uptake of weakly ionizing drugs by tumours is greatly influenced by the interstitial and intracellular pH, and the ionization properties of the drug. Extracellular pH in tumors is acidic, while the intracellular pH is in the neutral-to-alkaline range. Tumors of the bladder, kidney and gastrointestinal system in particular are exposed to extremes of pH. Strategies for exhancing and exploiting acid-outside plasmalemmal pH gradients to drive the uptake of weak acid drugs into tumors are discussed, as are techniques for alkalinizing tissues to improve response to weak base drugs. The participation of acidic intracellular vesicles in non-specific drug resistance is explored. (C) 2000 Harcourt Publishers Ltd.