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Project description:Diabetes commonly affects cancer patients. As a comorbidity, it may modify tumor biology and therapy response. Yet, we still lack an understanding of the diabetes-induced molecular changes in human breast tumors and their implication for therapy. The goal of this study was aimed to identify diabetes induced phenotypes and molecular signatures in breast cancer. Here, we investigated the effect 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 and hyperglycemia. Diabetes and hyperglycemia induced a mesenchymal and stem cell-like phenotypes. Further Diabetes and hyperglycemia also associated with oxidative stress and both gene expression and mutational signatures of DNA repair deficiency. Breast cancer cells cultured under hyperglycemia acquired increased DNA damage and sensitivity to DNA damage response inhibitors. Based on these observations, diabetes-associated breast tumors may show an increased drug response to DNA repair pathway inhibitors that are cancer therapeutics.
2023-11-07 | GSE202922 | GEO
Project description:Diabetes commonly affects cancer patients. As a comorbidity, it may modify tumor biology and therapy response. Yet, we still lack an understanding of the diabetes-induced molecular changes in human breast tumors and their implication for therapy. The goal of this study was aimed to identify diabetes induced phenotypes and molecular signatures in breast cancer. Here, we investigated the effect 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 and hyperglycemia. Diabetes and hyperglycemia induced a mesenchymal and stem cell-like phenotypes. Further Diabetes and hyperglycemia also associated with oxidative stress and both gene expression and mutational signatures of DNA repair deficiency. Breast cancer cells cultured under hyperglycemia acquired increased DNA damage and sensitivity to DNA damage response inhibitors. Based on these observations, diabetes-associated breast tumors may show an increased drug response to DNA repair pathway inhibitors that are cancer therapeutics.
2023-11-07 | GSE202599 | GEO
Project description:Diabetes commonly affects cancer patients. As a comorbidity, it may modify tumor biology and therapy response. Yet, we still lack an understanding of the diabetes-induced molecular changes in human breast tumors and their implication for therapy. The goal of this study was aimed to identify diabetes induced phenotypes and molecular signatures in breast cancer. Here, we investigated the effect 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 and hyperglycemia. Diabetes and hyperglycemia induced a mesenchymal and stem cell-like phenotypes. Further Diabetes and hyperglycemia also associated with oxidative stress and both gene expression and mutational signatures of DNA repair deficiency. Breast cancer cells cultured under hyperglycemia acquired increased DNA damage and sensitivity to DNA damage response inhibitors. Based on these observations, diabetes-associated breast tumors may show an increased drug response to DNA repair pathway inhibitors that are cancer therapeutics.
2023-11-07 | GSE236419 | GEO
Project description:Diabetes commonly affects cancer patients. As a comorbidity, it may modify tumor biology and therapy response. Yet, we still lack an understanding of the diabetes-induced molecular changes in human breast tumors and their implication for therapy. The goal of this study was aimed to identify diabetes induced phenotypes and molecular signatures in breast cancer. Here, we investigated the effect 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 and hyperglycemia. Diabetes and hyperglycemia induced a mesenchymal and stem cell-like phenotypes. Further Diabetes and hyperglycemia also associated with oxidative stress and both gene expression and mutational signatures of DNA repair deficiency. Breast cancer cells cultured under hyperglycemia acquired increased DNA damage and sensitivity to DNA damage response inhibitors. Based on these observations, diabetes-associated breast tumors may show an increased drug response to DNA repair pathway inhibitors that are cancer therapeutics.
2023-11-07 | GSE202598 | GEO
Project description:Diabetes commonly affects cancer patients. As a comorbidity, it may modify tumor biology and therapy response. Yet, we still lack an understanding of the diabetes-induced molecular changes in human breast tumors and their implication for therapy. The goal of this study was aimed to identify diabetes induced phenotypes and molecular signatures in breast cancer. Here, we investigated the effect 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 and hyperglycemia. Diabetes and hyperglycemia induced a mesenchymal and stem cell-like phenotypes. Further Diabetes and hyperglycemia also associated with oxidative stress and both gene expression and mutational signatures of DNA repair deficiency. Breast cancer cells cultured under hyperglycemia acquired increased DNA damage and sensitivity to DNA damage response inhibitors. Based on these observations, diabetes-associated breast tumors may show an increased drug response to DNA repair pathway inhibitors that are cancer therapeutics.
2023-11-07 | GSE202597 | GEO
Project description:Diabetes commonly affects cancer patients. As a comorbidity, it may modify tumor biology and therapy response. Yet, we still lack an understanding of the diabetes-induced molecular changes in human breast tumors and their implication for therapy. The goal of this study was aimed to identify diabetes induced phenotypes and molecular signatures in breast cancer. Here, we investigated the effect 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 and hyperglycemia. Diabetes and hyperglycemia induced a mesenchymal and stem cell-like phenotypes. Further Diabetes and hyperglycemia also associated with oxidative stress and both gene expression and mutational signatures of DNA repair deficiency. Breast cancer cells cultured under hyperglycemia acquired increased DNA damage and sensitivity to DNA damage response inhibitors. Based on these observations, diabetes-associated breast tumors may show an increased drug response to DNA repair pathway inhibitors that are cancer therapeutics.
2023-11-07 | GSE202595 | GEO
Project description:Diabetes commonly affects cancer patients. As a comorbidity, it may modify tumor biology and therapy response. Yet, we still lack an understanding of the diabetes-induced molecular changes in human breast tumors and their implication for therapy. The goal of this study was aimed to identify diabetes induced phenotypes and molecular signatures in breast cancer. Here, we investigated the effect 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 and hyperglycemia. Diabetes and hyperglycemia induced a mesenchymal and stem cell-like phenotypes. Further Diabetes and hyperglycemia also associated with oxidative stress and both gene expression and mutational signatures of DNA repair deficiency. Breast cancer cells cultured under hyperglycemia acquired increased DNA damage and sensitivity to DNA damage response inhibitors. Based on these observations, diabetes-associated breast tumors may show an increased drug response to DNA repair pathway inhibitors that are cancer therapeutics.
2023-11-07 | GSE236420 | GEO
Project description:Historically the development of anticancer treatments has been focused on their effect on tumor cells alone. However, newer treatments have shifted attention to targets on immune cells, resulting in dramatic responses. The effect of DNA repair deficiency on the microenvironment remains an area of key interest. Moreover, established therapies such as DNA damaging treatments such as chemotherapy and PARP inhibitors further modify the tumor microenvironment. Here we describe DNA repair pathways in breast cancer and activation of innate immune pathways in DNA repair deficiency, in particular, the STING (STimulator of INterferon Genes) pathway. Breast tumors with DNA repair deficiency are associated with upregulation of immune checkpoints including PD-L1 (Programmed Death Ligand-1) and may represent a target population for single agent or combination immunotherapy treatment.
| S-EPMC6607732 | biostudies-literature
Project description:Triple-negative breast cancer (TNBC) presents a marked diversity at the molecular level, which promotes a clinical heterogeneity that further complicates treatment. We performed a detailed whole exome sequencing profile of 29 Mexican patients with long follow-up TNBC to identify genomic alterations associated with overall survival (OS), disease-free survival (DFS), and pathologic complete response (PCR), with the aim to define their role as molecular predictive factors of treatment response and prognosis. We detected 31 driver genes with pathogenic mutations in TP53 (53%), BRCA1/2 (27%), CDKN1B (9%), PIK3CA (9%), and PTEN (9%), and 16 operative mutational signatures. Moreover, tumors with mutations in BRCA1/2 showed a trend of sensitivity to platinum salts. We found an association between deficiency in DNA repair and surveillance genes and DFS. Across all analyzed tumors we consistently found a heterogeneous molecular complexity in terms of allelic composition and operative mutational processes, which hampered the definition of molecular traits with clinical utility. This work contributes to the elucidation of the global molecular alterations of TNBC by providing accurate genomic data that may help forthcoming studies to improve treatment and survival. This is the first study that integrates genomic alterations with a long follow-up of clinical variables in a Latin American population that is an underrepresented ethnicity in most of the genomic studies.
| S-EPMC7699204 | biostudies-literature
Project description:BRCAness has important implications in the management and treatment of patients with breast and ovarian cancer. In this study, we propose a computational framework to measure the BRCAness of breast and ovarian tumor samples based on their gene expression profiles. We define a characteristic profile for BRCAness by comparing gene expression differences between BRCA1/2 mutant familial tumors and sporadic breast cancer tumors while adjusting for relevant clinical factors. With this BRCAness profile, our framework calculates sample-specific BRCA scores, which indicates homologous recombination (HR)-mediated DNA repair pathway activity of samples. We found that in sporadic breast cancer high BRCAness score is associated with aberrant copy number of HR genes rather than somatic mutation and other genomic features. Moreover, we observed significant correlations of BRCA score with genome instability and neoadjuvant chemotherapy. More importantly, BRCA score provides significant prognostic value in both breast and ovarian cancers after considering established clinical variables. In summary, the inferred BRCAness from our framework can be used as a robust biomarker for the prediction of prognosis and treatment response in breast and ovarian cancers.
| S-EPMC5691048 | biostudies-literature