MUC1 as a potential target in anticancer therapies.

Abstract

MUC1 is a glycoprotein that is overexpressed in tumor cells. In normal cells it forms a protective layer against microbes and toxic chemicals, besides providing lubrication on ductal surfaces. Oversecretion of MUC1 provide cancer cells with invasiveness, metastasis, and resistance to death induced by reactive oxygen species. MUC1 is made up of 2 heterodimers, MUC1-N and MUC1-C. MUC1-N is heavily glycosylated at 5 regions of the variable N-tandem repeats. MUC1-C is divisible into extracellular, intracellular, and cytoplasmic domain (MUC1-C/CD). The extracellular domain serves as a docking site for epidermal growth factor receptors and other receptor kinases; the transmembrane domain serves to relay messages from extracellular to MUC1-C/CD. The MUC1-C/CD has 5 phosphorylating sites that on interacting with the SH2 domain of specific proteins can stimulate tumor growth. Therapies targeting MUC1 consists of monoclonal antibodies (MAb), vaccines, or small molecules (aptamers). MAb therapies are mainly aimed at MUC1-N with little success, however, new generation of MAb are being developed for MUC1-C. Vaccines (peptide, carbohydrate, glycopeptide, DNA, and dendritic cell) have been developed that recognizes the aberrant glycosylated region of the variable N-tandem repeats in MUC1-N, whereas new generation vaccines are aimed at the cytoplasmic region of MUC1-C. Aptamers (peptides that resemble DNA, RNA) have been used for blocking the dimerization of CQC region and the 5 phosphorylating region of MUC1-C. In addition, aptamers have been used as cytotoxic drug carriers. However, none of the therapies for MUC1 are currently in clinical application, as they need further refinement and evaluation.

• Authors: Krishna Pillai, Mohammad H Pourgholami, Terence C Chua, David L Morris
• Journal: American journal of clinical oncology (Am J Clin Oncol) Vol. 38 Issue 1 Pg. 108-18 (Feb 2015) ISSN: 1537-453X [Electronic] United States
• PMID: 23608828 (Publication Type: Journal Article, Review)

Chemical References

• Antibodies, Monoclonal
• Aptamers, Nucleotide
• Cancer Vaccines
• MUC1 protein, human
• Mucin-1
• Neoplasm Proteins

Topics

• Antibodies, Monoclonal (therapeutic use)
• Aptamers, Nucleotide (therapeutic use)
• Cancer Vaccines (therapeutic use)
• Drug Resistance, Neoplasm
• Humans
• Molecular Targeted Therapy (methods)
• Mucin-1 (metabolism)
• Neoplasm Invasiveness
• Neoplasm Metastasis
• Neoplasm Proteins (metabolism)
• Neoplasms (drug therapy, metabolism, pathology)