Key enzymes and tumor cell heterogeneity.

Tumor heterogeneity is reflected in many aspects of cancer cells, including morphology, biology, drug responsiveness and biochemistry. The basis of the transformation- and progression-linked biochemical imbalance in cancer cells was revealed to be due to an imbalance in the activity, amount and isozyme pattern of key enzymes. The key enzymes, particularly those in the biosynthetic pathways of purine and pyrimidine metabolism, were identified as sensitive targets of experimental and clinical anticancer drugs. The concept of key enzymes as regulatory elements and targets of chemotherapy led to the design of enzyme-pattern-targeted anticancer chemotherapy approaches.