Recurrent disease following potentially curative surgery is the most common event causing death for patients with colorectal cancer. The identification of genetic events responsible for tumor recurrence in patients with stage II and III colon cancer could have a significant impact in upgrading current staging and treatment of these patients. The applicant's preliminary findings indicate that overexpression of thymidylate synthase (TS), an enzyme necessary for DNA synthesis, is a strong predictor for recurrence in patients with stage II colon cancer. In addition, he has found that in almost all tumors in which TS expression is increased, nuclear p53 is also overexpressed. In vitro data have confirmed the association between WAF1/CIP1 gene expression and p53 status. Furthermore, higher WAF1/CIP1 gene expression levels were associated with lower TS expression. The applicant proposes to expand his investigations to examine the relationship between TS expression and recurrence in patients with stage II and III colon cancer. He will determine WAF1/CIP1 expression and p53 status in the same specimens and correlate these findings to TS expression, recurrence and survival for patients with stage II and III colon cancer. If his hypothesis regarding the association of TS expression with recurrence is confirmed, current recommendations for patient care will change and if the relationship between WAF1/CIP1 with p53 status and TS expression is established, an important genetic determinant of colon tumor biology will be identified which might lead to new targets for therapy.
| Stoehlmacher, J; Ghaderi, V; Iobal, S et al. (2001) A polymorphism of the XRCC1 gene predicts for response to platinum based treatment in advanced colorectal cancer. Anticancer Res 21:3075-9 |
