MULTISTAGE CARCINOGENESIS AND THE CONCEPT OF ONCOGENE ADDICTION

It is now an axiom in oncology that human cancers often evolve through a multistage process that extends over decades. The marked increase in molecular biology studies within the past three decades has revealed that this multistage process is driven by the progressive accumula-tion of mutations and epigenetic abnormalities in expression of multiple genes that have highly diverse biochemical functions. Malignant carci-nomas of the lung, colon, breast, and other organ sites often display mutations in multiple oncogenes and tumor suppressor genes, harbor epigenetic abnormalities that result in increased or decreased expression of hundreds of genes, and contain chromosomal abnormalities tha