糖尿病通常影响癌症患者。我们采用三管齐下的方法研究了糖尿病对乳腺癌生物学的影响，包括分析原位人类肿瘤异种移植物、患者肿瘤和暴露于糖尿病/高血糖样条件的乳腺癌细胞。我们的目的是通过研究代谢组、转录组和肿瘤突变负荷来识别共有的表型和分子特征。糖尿病和高血糖不会增强细胞增殖，但会诱导间充质和干细胞样表型，从而增加细胞移动性和转移几率。它们还促进氧自由基的形成以及 DNA 修复缺陷的转​​录组和突变特征。此外，在糖尿病存在的情况下，食物和微生物组衍生的代谢物往往会积聚在乳腺肿瘤中，可能影响肿瘤生物学。在高血糖样条件下培养的乳腺癌细胞的 DNA 损伤和对 DNA 修复抑制剂的敏感性增加。基于这些观察，我们得出结论，与糖尿病相关的乳腺肿瘤可能表现出对 DNA 损伤修复抑制剂的药物反应增强。

Diabetes commonly affects cancer patients. We investigated the influence of diabetes on breast cancer biology using a three-pronged approach that included analysis of orthotopic human tumor xenografts, patient tumors, and breast cancer cells exposed to diabetes/hyperglycemia-like conditions. We aimed to identify shared phenotypes and molecular signatures by investigating the metabolome, transcriptome, and tumor mutational burden. Diabetes and hyperglycemia did not enhance cell proliferation but induced mesenchymal and stem cell-like phenotypes linked to increased mobility and odds of metastasis. They also promoted oxyradical formation and both a transcriptome and mutational signatures of DNA repair deficiency. Moreover, food- and microbiome-derived metabolites tended to accumulate in breast tumors in the presence of diabetes, potentially affecting tumor biology. Breast cancer cells cultured under hyperglycemia-like conditions acquired increased DNA damage and sensitivity to DNA repair inhibitors. Based on these observations, we conclude that diabetes-associated breast tumors may show an increased drug response to DNA damage repair inhibitors.