Grappling with Cancer

Abstract

One of the greatest challenges in the study of cancer has been confronting the mindset that the disease is too complex to address effectively: too many tissue types, too many etiologies, too much genetic chaos. In the 1970s, the oncogene concept provided temporary relief from this angst, because it was thought that a limited number of genes (proto-oncogenes), when activated through mutations, might turn a normal cell into a cancerous one. But what briefly seemed tidy quickly became messy again with the discovery of other classes of genes that normally protect against cancer. Most recently, advanced genome sequencing technologies have revealed a surprising fact: Every tumor contains hundreds to thousands of mutations, most of which affect only a small percentage of the cancers in any tumor type (see the Review by B. Vogelstein et al. , p. 1546). In addition, the high degree of cancer cell heterogeneity in each tumor suggests that we are studying a moving target that can readily dodge treatments through continual mutation. And the genetic uniqueness of every cancer raises the question of whether standardized cancer treatment protocols can ever achieve broad efficacy.