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Advanced Glycation End Products As a Potential Target for Restructuring the Ovarian Cancer Microenvironment: A Pilot Study

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.

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References
1.
Vlassara H, Valinsky J, Brownlee M, Cerami C, Nishimoto S, Cerami A . Advanced glycosylation endproducts on erythrocyte cell surface induce receptor-mediated phagocytosis by macrophages. A model for turnover of aging cells. J Exp Med. 1987; 166(2):539-49. PMC: 2189583. DOI: 10.1084/jem.166.2.539. View

2.
Cai B, Kasikara C, Doran A, Ramakrishnan R, Birge R, Tabas I . MerTK signaling in macrophages promotes the synthesis of inflammation resolution mediators by suppressing CaMKII activity. Sci Signal. 2018; 11(549). PMC: 6171110. DOI: 10.1126/scisignal.aar3721. View

3.
Gordon-Weeks A, Yuzhalin A . Cancer Extracellular Matrix Proteins Regulate Tumour Immunity. Cancers (Basel). 2020; 12(11). PMC: 7696558. DOI: 10.3390/cancers12113331. View

4.
Richardson M, Furlani R, Podell B, Ackart D, Haugen J, Melander R . Inhibition and breaking of advanced glycation end-products (AGEs) with bis-2-aminoimidazole derivatives. Tetrahedron Lett. 2015; 56(23):3406-3409. PMC: 4487526. DOI: 10.1016/j.tetlet.2015.01.122. View

5.
Singh V, Bali A, Singh N, Jaggi A . Advanced glycation end products and diabetic complications. Korean J Physiol Pharmacol. 2014; 18(1):1-14. PMC: 3951818. DOI: 10.4196/kjpp.2014.18.1.1. View