Landscaping the Cancer Terrain

Abstract
Colorectal cancer can arise as a result of spontaneous genetic lesions or an inherited defect. In this issue, Howe et al. report that the gene defective in one of the inherited syndromes is SMAD4, a member of a key signal transduction pathway. In their commentary, Kinzler and Vogelstein add this gene to a classification scheme for colorectal cancers that groups the offending genes as "gatekeepers," "caretakers," or "landscapers." Landscaping genes such as SMAD4 have an indirect effect on the tissue that will eventually become cancerous and create an abnormal microenvironment for the cells, probably by acting in the adjacent stromal cells.