4.3 Review

Drug resistance related to aberrant glycosylation in colorectal cancer

Journal

ONCOTARGET
Volume 9, Issue 1, Pages 1380-1402

Publisher

IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.22377

Keywords

drug therapy resistance mechanisms; cancer chemotherapy; cancer-associated glycosylations; glycosyltransferases; colorectal cancer

Funding

  1. Ligue Contre le Cancer/Comite du Nord
  2. Fondation ARC (Association pour la Recherche sur le Cancer)
  3. Region Nord-Pas de Calais (Cancer Regional Program)
  4. University of Lille
  5. Centre National de la Recherche Scientifique
  6. Ministere de l'Enseignement Superieur et de la Recherche

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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.

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