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

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

doi:10.3390/ijms24129804

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

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

School of Medicine

Research output: Contribution to journal › Article › peer-review

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.

Original language	English (US)
Article number	9804
Journal	International journal of molecular sciences
Volume	24
Issue number	12
DOIs	https://doi.org/10.3390/ijms24129804
State	Published - Jun 2023

Keywords

AGE breakers
ALT-711
Alagebrium
advanced glycation end product (AGE)
collagen
microenvironment
omentum
ovarian cancer

ASJC Scopus subject areas

Catalysis
Molecular Biology
Spectroscopy
Computer Science Applications
Physical and Theoretical Chemistry
Organic Chemistry
Inorganic Chemistry

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10.3390/ijms24129804

Cite this

Harper, E. I., Siroky, M. D., Hilliard, T. S., Dominique, G. M., Hammond, C., Liu, Y., Yang, J., Hubble, V. B., Walsh, D. J., Melander, R. J., Melander, C., Ravosa, M. J., & Stack, M. S. (2023). Advanced Glycation End Products as a Potential Target for Restructuring the Ovarian Cancer Microenvironment: A Pilot Study. International journal of molecular sciences, 24(12), Article 9804. https://doi.org/10.3390/ijms24129804

Harper, EI, Siroky, MD, Hilliard, TS, Dominique, GM, Hammond, C, Liu, Y, Yang, J, Hubble, VB, Walsh, DJ, Melander, RJ, Melander, C, Ravosa, MJ & Stack, MS 2023, 'Advanced Glycation End Products as a Potential Target for Restructuring the Ovarian Cancer Microenvironment: A Pilot Study', International journal of molecular sciences, vol. 24, no. 12, 9804. https://doi.org/10.3390/ijms24129804

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title = "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.",

keywords = "AGE breakers, ALT-711, Alagebrium, advanced glycation end product (AGE), collagen, microenvironment, omentum, ovarian cancer",

author = "Harper, {Elizabeth I.} and Siroky, {Michael D.} and Hilliard, {Tyvette S.} and Dominique, {Gena M.} and Catherine Hammond and Yueying Liu and Jing Yang and Hubble, {Veronica B.} and Walsh, {Danica J.} and Melander, {Roberta J.} and Christian Melander and Ravosa, {Matthew J.} and Stack, {M. Sharon}",

note = "Publisher Copyright: {\textcopyright} 2023 by the authors.",

year = "2023",

month = jun,

doi = "10.3390/ijms24129804",

language = "English (US)",

volume = "24",

journal = "International journal of molecular sciences",

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AU - Siroky, Michael D.

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AU - Dominique, Gena M.

AU - Hammond, Catherine

AU - Liu, Yueying

AU - Yang, Jing

AU - Hubble, Veronica B.

AU - Walsh, Danica J.

AU - Melander, Roberta J.

AU - Melander, Christian

AU - Ravosa, Matthew J.

AU - Stack, M. Sharon

PY - 2023/6

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N2 - 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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Advanced Glycation End Products as a Potential Target for Restructuring the Ovarian Cancer Microenvironment: A Pilot Study

Abstract

Keywords

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