The Impact of Sequencing Human Genome on Cancer Chemotherapy

This abstract describes the rational development of novel drugs design for treating cancers based on the information provided by the sequencing of Human Genome. Out of 24,000 genes in our Genome, sixteen thousand genes code for good proteins that keep us healthy. Six thousand mutated genes are identified which are responsible for causing six thousand different diseases including cancers. The most obvious approach is to design drugs to shut off mutated genes that code for wrong protein. Professor Ross was the first person to use a highly toxic chemical called Nitrogen Mustard developed during the World Wars to shut off a cancer-causing gene. Nitrogen Mustard can cross-link double stranded DNA and shut off a gene. Unfortunately, it has no selectivity. It cross-links all rapidly dividing cells both normal and abnormal cells. This abstract also describes the use of a novel class of drugs called Aziridines which acts as a Prodrug. It does not attack all dividing cells, Aziridines are activated in the presence of acid. As cancer cells grow rapidly, they use Glucose as a source of energy. In cancer cells, Glucose is broken down to produce Lactic Acid. It is the acid that activate Aziridine ring which opens to attack a single strand of DNA shutting off the genes. Over the years, we developed over a hundred analogs of Aziridines and tested against an experimental animal tumor called the Walker Carcinoma 256 in Rats. One compound, Aziridine dinitro-benzamide (CB1854) is found to be seventy times more toxic to cancer cell. Using the same rationale, we translated animal work in human making AZQ (US Patent 4,146,622 & 4,233,215) for treating Glioblastoma, a solid aggressive brain tumor in human. A new approach to treat Breast Cancer is also described.