title: Harnessing cancer cell metabolism for theranostic applications using metabolic glycoengineering of sialic acid in breast cancer as a pioneering example.
abstract: Abnormal cell surface display of sialic acids - a family of unusual 9-carbon sugars - is widely recognized as distinguishing feature of many types of cancer. Sialoglycans, however, typically cannot be identified with sufficiently high reproducibility and sensitivity to serve as clinically accepted biomarkers and similarly, almost all efforts to exploit cancer-specific differences in sialylation signatures for therapy remain in early stage development. In this report we provide an overview of important facets of glycosylation that contribute to cancer in general with a focus on breast cancer as an example of malignant disease characterized by aberrant sialylation. We then describe how cancer cells experience nutrient deprivation during oncogenesis and discuss how the resulting metabolic reprogramming, which endows breast cancer cells with the ability to obtain nutrients during scarcity, constitutes an "Achilles' heel" that we believe can be exploited by metabolic glycoengineering (MGE) strategies to develop new diagnostic methods and therapeutic approaches. In particular, we hypothesize that adaptations made by breast cancer cells that allow them to efficiently scavenge sialic acid during times of nutrient deprivation renders them vulnerable to MGE, which refers to the use of exogenously-supplied, non-natural monosaccharide analogues to modulate targeted aspects of glycosylation in living cells and animals. In specific, once non-natural sialosides are incorporated into the cancer "sialome" they can be exploited as epitopes for immunotherapy or as chemical tags for targeted delivery of imaging or therapeutic agents selectively to tumors.
authors.affiliation: Department of Biochemistry, Faculty of Agriculture, Zagazig University, Zagazig 44511, Egypt.
authors.forename: Haitham A
authors.initials: HA
authors.lastname: Badr
authors.affiliation: Department of Histology and Cytology, Faculty of Veterinary Medicine, Zagazig University, Zagazig 44511, Egypt.
authors.forename: Dina M M
authors.initials: DM
authors.lastname: AlSadek
authors.affiliation: Cancer Biology Department, National Cancer Institute, Cairo University, Cairo 11796, Egypt.
authors.forename: Motawa E
authors.initials: ME
authors.lastname: El-Houseini
authors.affiliation: Department of Biomedical Engineering and Translational Tissue Engineering Center, The Johns Hopkins University, Baltimore, MD 21231, USA.
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Saeui
authors.affiliation: Department of Biomedical Engineering and Translational Tissue Engineering Center, The Johns Hopkins University, Baltimore, MD 21231, USA.
authors.forename: Mohit P
authors.initials: MP
authors.lastname: Mathew
authors.affiliation: Department of Biomedical Engineering and Translational Tissue Engineering Center, The Johns Hopkins University, Baltimore, MD 21231, USA. Electronic address: kyarema1@jhu.edu.
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Yarema
authors.affiliation: GlycoMantra, Inc., Baltimore, MD 21227, USA. Electronic address: hfzahmed86@gmail.com.
authors.forename: Hafiz
authors.initials: H
authors.lastname: Ahmed
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism*; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D060847:Metabolic Engineering / Q000379:methods*; D019158:N-Acetylneuraminic Acid / Q000096:biosynthesis* / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D000068936:Theranostic Nanomedicine / Q000379:methods*
chemical_list: D006023:Glycoproteins; D009363:Neoplasm Proteins; D019158:N-Acetylneuraminic Acid
keywords: Biomarkers discovery; Cancer metabolism; Glycan sialylation; Metabolic glycoengineering; Nutrient deprivation; Nutrient utilization; Sialic acid glycoengineering