CCK Receptors and Cancer

Over the past 20 years there has been considerable interest in the role of CCK receptors in gastrointestinal cancer. Initial excitement over reports of the detection by PCR of CCK-1 and CCK-2 receptor mRNA in a wide range of gastrointestinal tumours has been tempered by the realisation that the presence of receptor binding sites is much more restricted. The current consensus is that expression of CCK-1 and -2 receptor proteins is common only in tumours of neural or neuroendocrine origin. A striking example of this general rule has been provided by the detection of CCK-2 receptors by receptor autoradiography in more than 90% of medullary thyroid carcinomas. Despite the absence of CCK receptors from many gastrointestinal adenocarcinomas, evidence from animal models and from tumour cell lines in vitro suggests that the CCK-2 receptor may contribute to the development of esophageal and gastric adenocarcinomas, and further experimental work in these areas is clearly warranted. Promising therapeutic approaches include the development of radiolabelled gastrin/CCK derivatives for use in tumour imaging, and the use of appropriate selective antagonists for treatment of those tumour subtypes likely to express CCK receptors.