Metformin and HER2-positive breast cancer: Mechanisms and therapeutic implications

Sara S Bashraheel; Hadeel Kheraldine; Sarah Khalaf; Ala-Eddin Al Moustafa

doi:10.1016/j.biopha.2023.114676

Metformin and HER2-positive breast cancer: Mechanisms and therapeutic implications

Biomed Pharmacother. 2023 Jun:162:114676. doi: 10.1016/j.biopha.2023.114676. Epub 2023 Apr 8.

Authors

Sara S Bashraheel¹, Hadeel Kheraldine², Sarah Khalaf³, Ala-Eddin Al Moustafa⁴

Affiliations

¹ QU Health, Qatar University, P.O. Box 2713, Doha, Qatar.
² College of Medicine, QU Health, Qatar University, P.O. Box 2713, Doha, Qatar.
³ College of Pharmacy, QU Health, Qatar University, P.O. Box 2713, Doha, Qatar.
⁴ College of Medicine, QU Health, Qatar University, P.O. Box 2713, Doha, Qatar; Biomedical Research Center, QU Health, Qatar University, PO. Box 2713, Doha, Qatar; Oncology Department, McGill University, Montreal, Quebec H3A 0G4, Canada. Electronic address: ala-eddinalmoustafa@mcgill.ca.

PMID: 37037091
DOI: 10.1016/j.biopha.2023.114676

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.

Keywords: Breast cancer; Diabetes; HER2; HER2/IGF-1R interaction; Metformin.

Publication types

Review

MeSH terms

AMP-Activated Protein Kinases / metabolism
Breast Neoplasms* / drug therapy
Diabetes Mellitus, Type 2* / drug therapy
Female
Humans
Hypoglycemic Agents / pharmacology
Metformin* / pharmacology

Substances

Metformin
AMP-Activated Protein Kinases
Hypoglycemic Agents