title: Molecular Pathways: Mucins and Drug Delivery in Cancer.
abstract: Over the past few decades, clinical and preclinical studies have clearly demonstrated the role of mucins in tumor development. It is well established that mucins form a barrier impeding drug access to target sites, leading to cancer chemoresistance. Recently gained knowledge regarding core enzyme synthesis has opened avenues to explore the possibility of disrupting mucin synthesis to improve drug efficacy. Cancer cells exploit aberrant mucin synthesis to efficiently mask the epithelial cells and ensure survival under hostile tumor microenvironment conditions. However, O-glycan synthesis enzyme core 2 beta 1,6 N-acetylglucosaminyltransferase (GCNT3/C2GnT-2) is overexpressed in Kras-driven mouse and human cancer, and inhibition of GCNT3 has been shown to disrupt mucin synthesis. This previously unrecognized developmental pathway might be responsible for aberrant mucin biosynthesis and chemoresistance. In thisMolecular Pathwaysarticle, we briefly discuss the potential role of mucin synthesis in cancers, ways to improve drug delivery and disrupt mucin mesh to overcome chemoresistance by targeting mucin synthesis, and the unique opportunity to target the GCNT3 pathway for the prevention and treatment of cancers.Clin Cancer Res; 23(6); 1373-8. ©2016 AACR.
authors.affiliation: Center for Cancer Prevention and Drug Development, Hematology and Oncology Section, Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma. altaf-mohammed@ouhsc.edu cv-rao@ouhsc.edu.
authors.forename: Chinthalapally V
authors.initials: CV
authors.lastname: Rao
authors.affiliation: Center for Cancer Prevention and Drug Development, Hematology and Oncology Section, Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma.
authors.forename: Naveena B
authors.initials: NB
authors.lastname: Janakiram
authors.affiliation: Center for Cancer Prevention and Drug Development, Hematology and Oncology Section, Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma. altaf-mohammed@ouhsc.edu cv-rao@ouhsc.edu.
authors.forename: Altaf
authors.initials: A
authors.lastname: Mohammed
mesh_terms: D000818:Animals; D016503:Drug Delivery Systems; D006801:Humans; D051379:Mice; D058990:Molecular Targeted Therapy; D009077:Mucins / Q000096:biosynthesis / Q000235:genetics*; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics*; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D011134:Polysaccharides / Q000096:biosynthesis; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D059016:Tumor Microenvironment / Q000235:genetics
chemical_list: C117307:KRAS protein, human; D009077:Mucins; D011134:Polysaccharides; D017351:N-Acetylglucosaminyltransferases; C117361:beta-1,3-galactosyl-O-glycosyl-glycoprotein beta-1,6-N-acetylglucosaminyltransferase 3; D016283:Proto-Oncogene Proteins p21(ras)