Molecular chemotherapy

For the past 50 years, during which chemotherapy has been administered for the treatment of cancer, the paradigm driving the selection of chemotherapeutic agents was their capability to damage the DNA of dividing cells. In addition, chemotherapeutic agents were studied for the selectivity of their toxic effect to the cancer cell versus the normal cell. Because many of the normal cells in the body shared the phenotype of cellular division with the tumor cells, the drugs developed for the treatment of cancer displayed only relative selectivity for the cancer cell. The advent of structural biology and computational chemistry to drug development, and the explosion of information about the molecular and genetic changes acquired in the cancer cell, have now produced the opportunity to design drugs for cancer treatment which specifically block the effects of the signals within cancer cells which drive the evolution of the disease process to unregulated cell growth. The implementation of this new mode of drug design to the field of cancer chemotherapy is the subject of this chapter.