Understanding molecular mechanisms in peritoneal dissemination of colorectal cancer

E. M. V. de Cuba, R. Kwakman, M. van Egmond, L. J. W. Bosch, H. J. Bonjer, G. A. Meijer, E. A. te Velde

When colorectal cancer (CRC) metastasizes, this is mostly to the liver via the portal circulation. In addition, 10-25 % of CRC patients eventually show metastases in the peritoneum. A selection of these patients is treated with cytoreductive surgery (CRS) and hyperthermic intra-peritoneal chemotherapy (HIPEC). However, several clinical needs still exist in which biomarkers could play an important role. Relatively little is known about the biology of peritoneal spread of CRC. The development of peritoneal metastases (PM) involves several steps, including: detachment of malignant cells; anoikis evasion; attachment to and invasion of the peritoneal surface ultimately ending in a colonization phase in which the malignant cells thrive in the newly formed niche. In this paper, we provide an overview of molecules associated with peritoneal dissemination and explore the clinical possibilities of these candidate biomarkers. A literature search was conducted using the PubMed database of the U.S. National Library of Medicine and Medline to identify studies on the biological behaviour of PM of CRC. In a series of over 100 studies on PM published between 1990 and 2010, IGF-1, HIF1α, VEGF, EGFR and ITGB1 emerge as the most interesting candidates for possible clinical application. Even though these promising candidate biomarkers have been identified, all of these require extensive further validation prior to clinical application. Yet, the pace of the omics revolution makes that the question is not if, but when biomarkers will be introduced to improve diagnosis and ultimately outcome of patients with PM due to CRC.