Drug resistance related to aberrant glycosylation in colorectal cancer

// Ninon Very 1 , Tony Lefebvre 1 and Ikram El Yazidi-Belkoura 1 1 Unité de Glycobiologie Structurale et Fonctionnelle, UGSF-UMR 8576 CNRS, Université de Lille, Lille 59000, France Correspondence to: Ikram El Yazidi-Belkoura, email: ikram.el-yazidi@univ-lille1.fr Keywords: drug therapy resistance mechanisms, cancer chemotherapy, cancer-associated glycosylations, glycosyltransferases, colorectal cancer Received: July 26, 2017 Accepted: October 04, 2017 Published: November 03, 2017 ABSTRACT Colorectal cancer (CRC) is the fourth leading cause of cancer-related deaths in the world. Drug resistance of tumour cells remains the main challenge toward curative treatments efficiency. Several epidemiologic studies link emergence and recurrence of this cancer to metabolic disorders. Glycosylation that modifies more than 80% of human proteins is one of the most widepread nutrient-sensitive post-translational modifications. Aberrant glycosylation participates in the development and progression of cancer. Thus, some of these glycan changes like carbohydrate antigen CA 19-9 (sialyl Lewis a, sLea) or those found on carcinoembryonic antigen (CEA) are already used as clinical biomarkers to detect and monitor CRC. The current review highlights emerging evidences accumulated mainly during the last decade that establish the role played by altered glycosylations in CRC drug resistance mechanisms that induce resistance to apoptosis and activation of signaling pathways, alter drug absorption and metabolism, and led to stemness acquisition. Knowledge in this field of investigation could aid to the development of better therapeutic approaches with new predictive biomarkers and targets tied in with adapted diet.