Integrated Biomedical Sciences Graduate Program, University of Notre Dame, Notre Dame, IN 46556, USA.
Department of Chemistry & Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA.
Int J Mol Sci. 2023 Jun 6;24(12):9804. doi: 10.3390/ijms24129804.
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.
卵巢癌是导致女性死亡的第六大癌症原因，60 岁以上女性的发病率和死亡率都有所上升。卵巢癌微环境中存在有记录的与年龄相关的变化，这些变化已经被证明可以创造一个允许转移的小生境，包括形成高级糖基化终产物（AGEs），这些产物在胶原蛋白分子之间形成交联。已经在其他疾病中研究了破坏 AGEs 的小分子，称为 AGE 断裂剂，但它们在卵巢癌中的疗效尚未得到评估。本研究的目的是针对肿瘤微环境中的与年龄相关的变化，以期改善老年患者的治疗反应。在这里，我们表明 AGE 断裂剂有可能改变大网膜胶原结构并调节腹膜免疫景观，这表明 AGE 断裂剂在卵巢癌治疗中有潜在的用途。
