Bashraheel Sara S, Kheraldine Hadeel, Khalaf Sarah, Moustafa Ala-Eddin Al
QU Health, Qatar University, P.O. Box 2713, Doha, Qatar.
College of Medicine, QU Health, Qatar University, P.O. Box 2713, Doha, Qatar.
Biomed Pharmacother. 2023 Jun;162:114676. doi: 10.1016/j.biopha.2023.114676. Epub 2023 Apr 8.
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.
由于糖尿病与癌症发生之间存在密切关联，包括二甲双胍在内的几种抗糖尿病药物已被研究其抗癌活性。二甲双胍是一种双胍类抗高血糖药物，用作II型糖尿病的一线药物。它通过影响不同的分子途径，如AMP诱导蛋白激酶（AMPK）依赖性和AMPK非依赖性途径来展现抗癌活性。此外，二甲双胍间接抑制胰岛素样生长因子-1受体（IGF-1R）信号传导，该信号传导在乳腺恶性肿瘤中高度激活。另一方面，乳腺癌是全球癌症相关发病和死亡的主要原因之一，其中人表皮生长因子受体阳性（HER2阳性）亚型是最具侵袭性的亚型之一，淋巴结转移率很高。在本综述中，我们总结了糖尿病与人类癌症之间的关联，列出了二甲双胍抗癌活性的最新证据。特别关注HER2阳性乳腺癌中HER2与IGF-1R之间的相互作用。然后，我们讨论二甲双胍与其他抗糖尿病药物在HER2阳性乳腺癌中的联合治疗策略。
