Cancer as a complex developmental disorder--nineteenth Cornelius P. Rhoads Memorial Award Lecture

The processes of differentiation and tumorigenesis have been long thought to be connected. The recent identification of Patched, a gene essential for Drosophila embryonic development, as a tumor suppressor has focused attention on the concept that tumorigenesis involves abnormalities of development. In fact, a large number of genes in the signalling pathway of the Patched gene are either tumor suppressors or oncogenes. This supports the concept that growth control is a critical requirement of differentiation, and that aberrant cellular development can contribute to malignancy. Whereas the identification of genes that result in dominantly inherited cancer syndromes has played a vital role in understanding cancer, the vast majority of "sporadic" cancers have properties of a complex genetic disease. Approaches to identify common alleles in cancer-associated genes promise to increase our understanding of the disease and aid the rational design of preventative and therapeutic strategies.