Advanced Glycation End Products as a Potential Target for Restructuring the Ovarian Cancer Microenvironment: A Pilot Study
-
Published:2023-06-06
Issue:12
Volume:24
Page:9804
-
ISSN:1422-0067
-
Container-title:International Journal of Molecular Sciences
-
language:en
-
Short-container-title:IJMS
Author:
Harper Elizabeth I.123, Siroky Michael D.23ORCID, Hilliard Tyvette S.23, Dominique Gena M.23, Hammond Catherine3, Liu Yueying23, Yang Jing23ORCID, Hubble Veronica B.2, Walsh Danica J.2ORCID, Melander Roberta J.2, Melander Christian2, Ravosa Matthew J.4, Stack M. Sharon23ORCID
Affiliation:
1. Integrated Biomedical Sciences Graduate Program, University of Notre Dame, Notre Dame, IN 46556, USA 2. Department of Chemistry & Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA 3. Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN 46617, USA 4. Center for Functional Anatomy and Evolution, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Abstract
Ovarian cancer is the sixth leading cause of cancer-related death in women, and both occurrence and mortality are increased in women over the age of 60. There are documented age-related changes in the ovarian cancer microenvironment that have been shown to create a permissive metastatic niche, including the formation of advanced glycation end products, or AGEs, that form crosslinks between collagen molecules. Small molecules that disrupt AGEs, known as AGE breakers, have been examined in other diseases, but their efficacy in ovarian cancer has not been evaluated. The goal of this pilot study is to target age-related changes in the tumor microenvironment with the long-term aim of improving response to therapy in older patients. Here, we show that AGE breakers have the potential to change the omental collagen structure and modulate the peritoneal immune landscape, suggesting a potential use for AGE breakers in the treatment of ovarian cancer.
Funder
National Institutes of Health Samuel Waxman Cancer Research Foundation Walther Cancer Foundation Cancer Cures Venture
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
Reference53 articles.
1. Howlader, N., Noone, A., Krapcho, M., Miller, D., Brest, A., Yu, M., Ruhl, J., Tatlovich, Z., Mariotto, A., and Lewis, D. (2019). SEER Cancer Statistics Review, 1975–2017. 2. Ovarian Cancer Development and Metastasis;Lengyel;Am. J. Pathol.,2010 3. Milky Spots: Omental Functional Units and Hotbeds for Peritoneal Cancer Metastasis;Liu;Tumor Biol.,2016 4. Harper, E.I., Sheedy, E.F., and Stack, M.S. (2018). With Great Age Comes Great Metastatic Ability: Ovarian Cancer and the Appeal of the Aging Peritoneal Microenvironment. Cancers, 10. 5. Another Wrinkle with Age: Aged Collagen and Intra-Peritoneal Metastasis of Ovarian Cancer;Harper;Aging Cancer,2022
|
|