James Trosko, College of Human Medicine, Michigan State University
A paradign challenge in understanding carcinogenesis: adult stem cells and cell-cell communication gone amuck

Can anyone understand how to prevent or treat cancer when we are all exposed to so many contradictory hypotheses and experimental/epidemiological observations? Recently, an attempt to highlight universal properties or � Hallmarks of cancer� has been made [Hanahan and Weinberg, Cell 100: 57-70, 2000 ]. While an excellent start to test these hypotheses, several concepts have been ignored which have set the stage for a new paradigm to emerge. In the evolution of any scientific theory in any discipline, the scope and validity of the scientific data and methodology, as well as the nature of the paradigms used to interpret the data, need to be critically examined. It is a fact that the genesis of a cancer is a multi-step, multi-mechanism process, involving one�s genetic background, gender, developmental stage, dietary and medical background, workplace experience and lifestyle. Both genes and environmental factors (radiations; chemicals; and biological agents[ viruses and bacteria]) interact to contribute to the various stages of carcinogenesis [ e.g., �initiation�; �promotion�; �progression� phases]. Two ignored old concepts (The adult stem cell as a target for �initiating� the process; and cell-cell communication between this �initiated� cell and the surrounding normal cells) will be integrated into a new paradigm of carcinogenesis [Trosko etc. �Oct4 expression in adult human stem cells: evidence in support of the stem cell theory of carcinogenesis�. Carcinogenesis, in press]. This new paradigm should assist in more efficacious strategies for prevention and treatment of cancer and give support to another unifying concept that the mechanisms associated with chronic irritation is a shared process of many chronic diseases (cancer; atherosclerosis; diabetes; chronic bowel disease; Alzheimer�s disease; cataracts, etc.)