Changes in insulin receptor signaling underlie neoadjuvant metformin administration in breast cancer: a prospective window of opportunity neoadjuvant study
| العنوان: | Changes in insulin receptor signaling underlie neoadjuvant metformin administration in breast cancer: a prospective window of opportunity neoadjuvant study |
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| المؤلفون: | Marguerite Ennis, Susan J. Done, David R. McCready, Ryan J.O. Dowling, Michael Reedijk, Martin C. Chang, Vuk Stambolic, Jaime Escallon, Pamela J. Goodwin, Wey L. Leong, Saroj Niraula |
| المصدر: | Breast Cancer Research : BCR |
| بيانات النشر: | Springer Nature |
| مصطلحات موضوعية: | Adult, endocrine system diseases, medicine.medical_treatment, Antineoplastic Agents, Breast Neoplasms, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Diabetes mellitus, medicine, Humans, Phosphorylation, Protein kinase B, Neoadjuvant therapy, 030304 developmental biology, Aged, Neoplasm Staging, Mitogen-Activated Protein Kinase 1, Medicine(all), 0303 health sciences, Mitogen-Activated Protein Kinase 3, biology, business.industry, Insulin, AMPK, nutritional and metabolic diseases, Middle Aged, medicine.disease, Metformin, Neoadjuvant Therapy, Receptor, Insulin, 3. Good health, Insulin receptor, Editorial, 030220 oncology & carcinogenesis, biology.protein, Cancer research, Female, Neoplasm Grading, business, Proto-Oncogene Proteins c-akt, Biomarkers, medicine.drug, Signal Transduction |
| الوصف: | The antidiabetic drug metformin exhibits potential anticancer properties that are believed to involve both direct (insulin-independent) and indirect (insulin-dependent) actions. Direct effects are linked to activation of AMP-activated protein kinase (AMPK) and an inhibition of mammalian target of rapamycin mTOR signaling, and indirect effects are mediated by reductions in circulating insulin, leading to reduced insulin receptor (IR)-mediated signaling. However, the in vivo impact of metformin on cancer cell signaling and the factors governing sensitivity in patients remain unknown. We conducted a neoadjuvant, single-arm, “window of opportunity” trial to examine the clinical and biological effects of metformin on patients with breast cancer. Women with untreated breast cancer who did not have diabetes were given 500 mg of metformin three times daily for ≥2 weeks after diagnostic biopsy until surgery. Fasting blood and tumor samples were collected at diagnosis and surgery. Blood glucose and insulin were assayed to assess the physiologic effects of metformin, and immunohistochemical analysis of tumors was used to characterize cellular markers before and after treatment. Levels of IR expression decreased significantly in tumors (P = 0.04), as did the phosphorylation status of protein kinase B (PKB)/Akt (S473), extracellular signal-regulated kinase 1/2 (ERK1/2, T202/Y204), AMPK (T172) and acetyl coenzyme A carboxylase (S79) (P = 0.0001, P |
| اللغة: | English |
| تدمد: | 1465-542X 0089-7884 |
| DOI: | 10.1186/s13058-015-0540-0 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::720911341e2b56ba86ff8eba29b9a185Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....720911341e2b56ba86ff8eba29b9a185 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 1465542X 00897884 |
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| DOI: | 10.1186/s13058-015-0540-0 |