Oncogenes and the initiation and maintenance of tumorigenesis

Cancer is a complex and multistep process whereby an individual cell acquires a series of mutant gene products culminating in a spectrum of pathophysiologic features including relentless proliferation, growth, blocked differentiation, the inappropriate induction of angiogenesis, tissue invasion, and loss of genomic stability. Given the genetic and biologic complexity of tumorigenesis, it is perhaps surprising that there are circumstances when cancer can be reversed through the repair or inactivation of individual mutant genes. However, recent experiments in transgenic mouse models and clinical results using new pharmacological agents demonstrate that cancer can be treated through the targeted repair and/or inactivation of specific oncogenes. Hence, cancers appear to be dependent upon particular oncogenes to maintain their neoplastic properties, thus exhibiting the phenomena tumor maintenance or oncogene addiction.