Of all the known cancers, oral cancer is the most preventable and it is the second most deadly cancer after the breast cancer. Out of 609,640 deaths of overall cancers, 13,500 died of oral cancer. In spite of this enormous increase in loss of life, there are no useful drugs to treat oral cancer. Sequencing human genome identifies with precision and accuracy the specific mutations responsible for causing oral cancer. In this chapter, a novel approach to design drugs to attack mutated genes in squamous cell carcinoma responsible for causing oral cancer is proposed. Alkylating aziridines attack single-stranded DNA shutting off genes. Using dinitrobenzamide dye as a carrier for aziridine, we successfully made a novel class of drugs (CB 1954) which shuts off gene of a solid tumor, Walker Carcinoma 256, in rats. We translated the animal work in humans by using quinone as a carrier for aziridines making AZQ (US Patent 4,146,622) for attacking glioblastoma for treating brain cancer in humans. We propose to search for a carrier for aziridines to attack squamous cell carcinomas to treat oral cancer. Ethical issues are discussed. Since tobacco smoking causes oral cancer, it is the most preventable disease.
Part of the book: Prevention, Detection and Management of Oral Cancer
Professor Ross of London University, England, was using nitrogen mustard to treat cancers by attacking both strands of tumor DNA. As a part of my doctoral thesis, I am to design drugs using aziridine to attack only one strand of DNA. Over the years, I made over 100 dinitrophenyl aziridine derivatives. One of them is dinitrobenzamide (CB1954) which gives a CI of 70, highest toxicity to animal tumor ever recorded. CB1954 wipes out a solid aggressive tumor by attacking a single-strand DNA of Walker carcinoma 256, in rat. My greatest challenge at NCI in USA is to translate the animal work which I did in London University to humans. As radiolabeled methylated quinone crosses the blood-brain barrier in mice, I decided to use quinone moiety as a carrier for aziridine rings to attack glioblastomas, the brain tumor in humans. By attaching two aziridines and two carbamate moieties to quinone, I made AZQ (US Patent 4,146,622). By treating brain cancer with AZQ , we observed that glioblastoma tumor not only stops growing but also starts shrinking. Literature search showed that AZQ is extensively studied.
Part of the book: Drug Design