Abstract
Female breast cancer is a complex, multifactorial disease. Studies have shown that hyperglycemia is one of the most important contributing factors to increasing the risk of breast cancer that also has a major impact on the efficacy of chemotherapy. At the cellular level, hyperglycemia can promote the proliferation, invasion, and migration of breast cancer cells and can also induce anti-apoptotic responses to enhance the chemoresistance of tumors via abnormal glucose metabolism. In this article, we focus on the latest progress in defining the mechanisms of chemotherapy resistance in hyperglycemic patients including the abnormal behaviors of cancer cells in the hyperglycemic microenvironment and the impact of abnormal glucose metabolism on key signaling pathways. To better understand the advantages and challenges of breast cancer treatments, we explore the causes of drug resistance in hyperglycemic patients that may help to better inform the development of effective treatments.
Highlights
Breast cancer (BC) is the most common malignancy in women all over the world [1] and has several known risk factors including age, sex, obesity, estrogen levels, and family history [2]
The reprogramming of glucose metabolism accelerates the conversion of glycolysis and changes the acidity of the Hyperglycemia and Chemoresistance in Breast Cancer microenvironment which acts to promote the expression of angiogenic factors and enhance tumor metastasis [9]
Recent studies have shown that somatic and BC cells from patients with hyperglycemia or metabolic abnormalities have elevated acidity in the TUMOR MICROENVIRONMENT (TME) accompanied by increased reactive oxygen species (ROS) and other changes in energy homeostasis
Summary
Breast cancer (BC) is the most common malignancy in women all over the world [1] and has several known risk factors including age, sex, obesity, estrogen levels, and family history [2]. They showed that these cells are non-proliferate but can significantly regulate the TME by elevating levels of ROS and by stabilizing HIF-1 These processes contribute to increased levels of vascular endothelial growth factor (VEGF) and macrophage migration inhibitory factor (MIF) and can induce chemotherapeutic resistance by upregulating anti-apoptotic proteins through the RAS/MAPK pathway [75]. Metformin can alter cancer metabolism and mitochondrial function It can regulate key signaling pathways such as the Ras/Raf MEK/ERK PI3K/Akt and mTOR pathways to increase cell death and inhibit many cellular processes including proliferation, migration, EMT, invasion, and metastasis [83]. Metformin changes signal transmission of the Warburg effect during tumor development and can inhibit glucose uptake by cancer cells [84] It reduces circulating hormone levels, estrogens, that are associated with the development of postmenopausal BC [85]. The METEOR study provides evidence of the neoadjuvant metformin plus letrozole for anti-tumor effects in non-diabetic postmenopausal ER-positive patients [91]
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