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Combinational strategies of metformin and chemotherapy in cancers

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Abstract

Chemotherapeutic regimens are the most common treatment to inhibit tumor growth, but there is great variability in clinical responses of cancer patients; cancer cells often develop resistance to chemotherapeutics which results in tumor recurrence and further progression. Metformin, an extensively prescribed and well-tolerated first-line therapeutic drug for type 2 diabetes mellitus, has recently been identified as a potential and attractive anticancer adjuvant drug combined with chemotherapeutic drugs to improve treatment efficacy and lower doses. In this review, we summarized the molecular mechanisms underlying anticancer effects of metformin, which included insulin- and AMPK-dependent effects, selectively targeting cancer stem cells, reversing multidrug resistance, inhibition of the tumor metastasis and described the antineoplastic effects of metformin combined with chemotherapeutic agents in digestive system cancers (colorectal, gastric, hepatic and pancreatic cancer), reproductive system cancers (ovarian and endometrial cancer), prostate cancer, breast cancer, lung cancer, etc. Moreover, the clinical trials regarding metformin in combination of chemotherapeutic drugs were presented and the clinical obstacle or limitation related to the potential role of metformin in cancer treatment was also discussed in this review.

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Acknowledgments

This work was funded by the National Science Foundation of China Grants (81373450) and Shandong Province Science and Technology Key Project (2014GSF118032).

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  1. Department of Pharmacology, School of Pharmaceutical Sciences, Shandong University, No. 44 Wen Hua Xi Road, Jinan, 250012, People’s Republic of China

    Hui-Hui Zhang & Xiu-Li Guo

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Correspondence to Xiu-Li Guo.

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Zhang, HH., Guo, XL. Combinational strategies of metformin and chemotherapy in cancers. Cancer Chemother Pharmacol 78, 13–26 (2016). https://doi.org/10.1007/s00280-016-3037-3

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