Molecular basis of multistage carcinogenesis.
Revealing the molecular basis of human disease including cancer will be viewed as one of the triumphs of biomedical research in the 20th Century. One successful strategy has been to analyze abnormalities in cancer-related genes occurring in preneoplastic and neoplastic lesions in humans and animal models. These gene abnormalities, e.g., mutations, can be specifically linked in some cases to environmental carcinogens in molecular epidemiological studies of human populations and in more controlled experimental conditions using animal or in vitro models of carcinogenesis. A second successful strategy has been to capitalize on advances from basic research such as defining signal transduction pathways in mammalian cells and the genetic control of the cell cycle in yeast. Mutations in yeast cell division control genes can lead to genomic instability and aneuploidy which are hallmarks of cancer. Therefore, the role of these genes in human carcinogenesis is being intensely investigated. The involvement of the p53 gene in the majority of human cancers has focused attention on the molecular and biochemical mechanisms of this tumor suppressor gene. The analysis of the p53 mutational spectrum in human cancers has provided evidence that both exogenous and endogenous causes of mutation contribute to human carcinogenesis. The increased understanding of the molecular basis of carcinogenesis has important implications in the prevention, diagnosis and treatment of human cancer.
Harris
C C
CC
Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
D000818:Animals; D003043:Cocarcinogenesis; D016147:Genes, Tumor Suppressor; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000209:etiology* / Q000235:genetics; D011519:Proto-Oncogenes