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

晚期糖基化终产物作为重构卵巢癌微环境的潜在靶点:一项初步研究

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作者:Elizabeth I Harper, Michael D Siroky, Tyvette S Hilliard, Gena M Dominique, Catherine Hammond, Yueying Liu, Jing Yang, Veronica B Hubble, Danica J Walsh, Roberta J Melander, Christian Melander, Matthew J Ravosa, M Sharon Stack

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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