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The Biology of the Deadly Love Connection Between Obesity, Diabetes, and Breast Cancer

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Breast Cancer Metastasis and Drug Resistance

Abstract

Breast cancer is the most common malignant disease of women in the world and a leading cause of women’s deaths. Many risk factors such as genetics, hormones, aging, and environment have been associated with breast cancer. Interestingly, a large number of epidemiological and clinical studies suggest that obesity and diabetes, especially type-2 diabetes, are associated with higher risk of breast cancer. Similarly, these chronic diseases, such as obesity, diabetes, and cancer, are also a major public health concern in the world. Fifty percent of the United States’ population is overweight, thirty percent is obese, and ten percent has diabetes mellitus. Therefore, obesity and diabetes mellitus have been considered as potential risk factors for many cancers but this chapter is focused only on breast cancer. Although the mechanisms responsible for the development of these chronic diseases leading to the development of breast cancer are not fully understood, the biological importance of the activation of insulin, insulin like growth factor-1 (IGF-1) and its receptor (IGF-1R) signaling pathways in insulin-resistance mechanism and subsequent induction of compensatory hyperinsulinemia has been proposed. Therefore, targeting insulin/IGF-1 signaling with anti-diabetic drugs for lowering blood insulin levels and reversal of insulin-resistance could be a useful strategy for the prevention and/or treatment of breast cancer. Increased numbers of clinical studies have demonstrated that the administration of commonly used anti-diabetic drugs such as metformin decreases the risk of cancers, suggesting that these agents might be useful anti-tumor agents for the treatment of breast cancer. In this chapter, we will discuss the potential roles of anti-diabetic drug metformin as anti-tumor agents in the context of breast cancer, and will further discuss the potential roles of microRNAs (miRNAs) in the pathogenesis of obesity, diabetes, and breast cancer.

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Acknowledgments

We thank Puschelberg and Guido foundations for their generous financial contribution. We also thank Ms. Ahmedi Bee Fnu and Mr. Evan Bao for the technical assistance.

Grant Support: National Cancer Institute, NIH grants 5R01CA131151, 5R01CA132794 and 1R01CA154321 (F.H. Sarkar), DOD Exploration-Hypothesis Development Award PC101482 (B Bao).

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  1. Department of Pathology, Karmanos Cancer Institute, Wayne State University School of Medicine, 740 Hudson Webber Cancer Research Center, 4100 JohnR Street, Detroit, MI, 48201, USA

    Bin Bao, Anthony Oraha, Aamir Ahmad, Yiwei Li, Asfar S. Azmi, Sanjeev Banerjee & Fazlul H. Sarkar

  2. Departments of Pathology and Oncology, Karmanos Cancer Institute, Wayne State University School of Medicine, 740 Hudson Webber Cancer Research Center, 4100 JohnR Street, Detroit, MI, 48201, USA

    Shadan Ali & Fazlul H. Sarkar

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    Aamir Ahmad

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Bao, B. et al. (2013). The Biology of the Deadly Love Connection Between Obesity, Diabetes, and Breast Cancer. In: Ahmad, A. (eds) Breast Cancer Metastasis and Drug Resistance. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-5647-6_7

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