Exploiting genetic alterations to design novel therapies for cancer

Cancer is a genetic disease, arising as a result of genetic mutations that endow the cell with many specific functional capabilities.(43) Individual m utations may accumulate over time that summarily lead to all of the capabil ities (84) likely accounting for the increased incidence of cancer with age . Alternatively the cancerous phenotype may result from only one or a few s eminal genetic events that have multifunctional consequences, such as mutat ion of transcription factor genes, a theme common among childhood cancers.( 41, 61, 72) The latter mechanism may give rise to cancers that occur in chi ldhood because decades are not required to accumulate the requisite cadre o f mutations. Therapies aimed at such pivotal events similarly might have mu ltifactorial effects. To contemplate exploiting genetic mutations for therapy, it is imperative t o understand molecular details of cancer-associated gene mutations. A categ orization of the various mechanisms of gene mutations uncovered in pediatri c cancers is summarized in Table 1. Interventions based on these mutations fall into three broad areas: gene manipulation, viral oncolysis, and immuno therapy. These fields are relatively new and speculative by nature. Conside ration of early successes in vitro and in animal models combined with the b road range of strategies being explored warrants optimism that at least som e of these efforts will be fruitful.