5th World Congress on Cancer Therapy
Chiba University, Japan
Title: Target genes for acidosis-dependent anti-cancer drugsv
Biography: Hiroshi Kobayashi
While mammalian blood and normal tissues are usually maintained at pH around 7.4, the extracellular pH drops below 6.5 in solid cancer nests. Enzymes which function preferentially at acidic pH may be the target molecules of anti-cancer drugs. Our group have found that the inhibition of protein prenylation attenuates proliferation of cancer cells at acidic pH, suggesting that an enzyme(s) to prenylate proteins is functioning under acidic conditions. In addition to the enzyme for protein prenylation, there may be other enzymes functioning under acidic conditions. To fi nd such enzymes, the expression of 24,000 genes was examined using a DNA array chip in mesothelioma cells, and the expression of approximately 700 genes was elevated at acidic pH. Th e elevated expression of these genes was found in other cancer cells grown under acidic conditions and in human specimens from cancer patients. Th ese results suggest that mammalian cells have many enzymes which function preferentially in acidic cancer nests, and that drugs inhibiting these enzymes could be potent candidates for anticancer chemotherapeutics with less side-eff ect, especially on immune systems in blood and normal tissues, because acidosisdependent drugs are expected to be less eff ective in tissues whose pH is alkaline. In fact, inhibitors of protein prenylation had little eff ect on proliferation and cytokine production of immune cells at alkaline pH. Th e screening under acidic conditions may be a useful way to fi nd new anti-cancer drugs which are eff ective in acidic cancer nests.