ABSTRACT
INTRODUCTION Oncogene Addiction and Driver Mutation Human cancers usually evolve through multistep processes that can extend over a period of decades. This process is driven by the accumulation of genetic and epigenetic abnormalities in multiple genes that have highly diverse functions. In contrast to multistep tumorigenesis, the “oncogene addiction” model proposes that some cancers develop through genetic alternation, including mutation, of one gene.1 These mutations induce and sustain tumorigenesis, and can be thus referred to as “driver mutations.” These cancers are reliant upon the protein product of this gene for their malignant phenotype. In these tumors, targeting this protein, or “Achilles heel” of the cancer, can profoundly inhibit its growth and result in patient benefi t. Support for this oncogene addiction model comes from the increasing number of examples of the therapeutic effi cacy of drugs that target specifi c oncogenes in human cancers including epidermal growth factor receptor (EGFR) in EGFR mutant lung cancer.
