Lay Summary

Proposal No.   IBD-0068R
Principal Investigator:  Christine Cartwright, M.D.
Applicant Organization:  Stanford University (California, U.S.A.)
Project Title: Ulcerative colitis: molecular mechanisms of carcinogenesis
Period of Award:  September 1, 2003 - March 31, 2006

Longstanding, extensive ulcerative colitis (UC) carries an increased risk of colon cancer. The risk of developing cancer is fifteen-fold higher, and the risk of dying from cancer is five-fold higher than expected in age-matched populations without colitis. Moreover, colon cancer accounts for about one-third of UC deaths. Thus, colon cancer is a major cause of morbidity and mortality in UC.  Ninety percent of all colon cancer cases and deaths are preventable. If detected at an early stage, the cancer is curable; if detected at a late stage, death occurs within months. Thus, we need to define early molecular mechanisms involved in the genesis of UC colon cancer. Only then can we proceed with development of new strategies for prevention, early detection and treatment.

This proposal addresses molecular mechanisms by which UC colon cancer arises and whether these mechanisms are in common with those involved in the genesis of sporadic colon cancer. Our goal is to identify early events that perturb normal regulatory pathways in pre-cancerous cells. UC colon cancers are thought to arise from areas of pre-cancer within the affected region of the colon. However, the precise molecular and cellular basis for UC colon cancer is unclear. Although much is known about molecular events underlying the progression from pre-cancer to cancer in sporadic colon cancer, relatively little is known about these events in the development of UC colon cancer.

Activation of the cancer gene Src has been implicated in the development of UC colon cancer. We propose to define the molecular mechanisms by which Src is activated and to assess the influence of Src activation on the development of UC colon cancer. The results of these studies could lead to development of new molecular markers and novel, more selective therapy for UC colon cancer.