Gastrin, gastrin receptors and colorectal carcinoma

Abstract

Most colorectal carcinomas produce progastrin, but only a subset of colorectal carcinomas expresses classic gastrin/CCK-B receptors. Novel gastrin/CCK receptors capable of binding non-amidated forms of progastrin derived peptides have also been described in the past three years. High affinity antagonists selective for the non-classic gastrin/CCK receptors are required urgently, in order to test the working hypothesis that one or more of the novel receptors is the target for the autocrine proliferative effects of progastrin derived peptides. In the longer term the interaction between progastrin derived peptides and the proteins altered by the cascade of genetic mutations associated with the development of colorectal carcinoma60 needs to be resolved. Demonstration of proliferative effects of progastrin derived peptides in the early stages of the adenomacarcinoma sequence might have diagnostic and therapeutic benefits.