Diabetes-associated breast cancer is molecularly distinct and shows a DNA damage repair deficiency

• DOI: 10.1172/jci.insight.170105
• Publication Date: 2023-10-31T16:00:54Z
• Authors: Gatikrushna Panig...; Julián Candia; Tiffany H. Dorsey; Wei Tang; Yuuki Ohara; Jung S. Byun; Tsion Zewdu Minas; Amy Zhang; Anuoluwapo Ajao; Ashley Cellini; Harris G. Yfantis; Amy L. Flis; Dean Mann; Olga Ioffe; Xin W. Wang; Huaitian Liu; Christopher A. Lo...; Anna Maria Napoles; Stefan Ambs
• Keywords: DNA Repair; Hyperglycemia; Diabetes Mellitus; Humans; Female; Breast Neoplasms; 3. Good health; Research Article; DNA Damage

Diabetes commonly affects patients with cancer. We investigated the influence of diabetes on breast cancer biology using a 3-pronged approach that included analysis orthotopic human tumor xenografts, patient tumors, and cells exposed to diabetes/hyperglycemia-like conditions. aimed identify shared phenotypes molecular signatures by investigating metabolome, transcriptome, mutational burden. hyperglycemia did not enhance cell proliferation but induced mesenchymal stem cell-like linked increased mobility odds metastasis. They also promoted oxyradical formation both transcriptome DNA repair deficiency. Moreover, food- microbiome-derived metabolites tended accumulate in tumors presence diabetes, potentially affecting biology. Breast cultured under hyperglycemia-like conditions acquired damage sensitivity inhibitors. Based these observations, we conclude diabetes-associated may show an drug response