Metformin and HER2-positive breast cancer: Mechanisms and therapeutic implications
Bibliographic record
Abstract
Due to the strong association between diabetes and cancer incidents, several anti-diabetic drugs, including metformin, have been examined for their anticancer activity. Metformin is a biguanide antihyperglycemic agent used as a first-line drug for type II diabetes mellitus. It exhibits anticancer activity by impacting different molecular pathways, such as AMP-inducible protein kinase (AMPK)-dependent and AMPK-independent pathways. Additionally, Metformin indirectly inhibits IGF-1R signaling, which is highly activated in breast malignancy. On the other hand, breast cancer is one of the major causes of cancer-related morbidity and mortality worldwide, where the human epidermal growth factor receptor-positive (HER2-positive) subtype is one of the most aggressive ones with a high rate of lymph node metastasis. In this review, we summarize the association between diabetes and human cancer, listing recent evidence of metformin's anticancer activity. A special focus is dedicated to HER2-positive breast cancer with regards to the interaction between HER2 and IGF-1R. Then, we discuss combination therapy strategies of metformin and other anti-diabetic drugs in HER2-positive breast cancer.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".