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Diabetes increases the risk of breast cancer, but the mechanisms behind this heightened risk, especially for metastasis, are still being uncovered.

In this recent study, Zhou et al. investigated the role of advanced glycation end products (AGEs), which are elevated in diabetic patients, in promoting breast cancer spread. Using a combination of in vitro cell culture studies and in vivo mouse models, the researchers demonstrated that AGEs interact with their receptor (RAGE) on breast cancer cells, leading to the demethylation of the MMP-9 gene promoter, which is critical for tumour invasion and metastasis. Through detailed molecular experiments, they identified that this process is mediated by the GADD45α protein, which facilitates DNA demethylation through a base excision repair pathway.

This study underscores a novel epigenetic mechanism linking diabetes to cancer metastasis, and also shows how metabolic changes in diabetes can drive more aggressive cancer behaviour. It offers diabetologists valuable insights into the intersection of diabetes and cancer, and highlights how targeting the AGE–RAGE axis could be a new therapeutic strategy for treating cancer in patients with diabetes.

Read the full article in Endocrine-Related Cancer 31 e230330 https://doi.org/10.1530/ERC-23-0330