Potential Therapies Targeting the Metabolic Reprogramming of Diabetes-Associated Breast Cancer

Abstract

In recent years, diabetes-associated breast cancer has become a significant clinical challenge. Diabetes is not only a risk factor for breast cancer but also worsens its prognosis. Patients with diabetes usually show hyperglycemia and hyperinsulinemia, which are accompanied by different glucose, protein, and lipid metabolism disorders. Metabolic abnormalities observed in diabetes can induce the occurrence and development of breast cancer. The changes in substrate availability and hormone environment not only create a favorable metabolic environment for tumorigenesis but also induce metabolic reprogramming events required for breast cancer cell transformation. Metabolic reprogramming is the basis for the development, swift proliferation, and survival of cancer cells. Metabolism must also be reprogrammed to support the energy requirements of the biosynthetic processes in cancer cells. In addition, metabolic reprogramming is essential to enable cancer cells to overcome apoptosis signals and promote invasion and metastasis. This review aims to describe the major metabolic changes in diabetes and outline how cancer cells can use cellular metabolic changes to drive abnormal growth and proliferation. We will specifically examine the mechanism of metabolic reprogramming by which diabetes may promote the development of breast cancer, focusing on the role of glucose metabolism, amino acid metabolism, and lipid metabolism in this process and potential therapeutic targets. Although diabetes-associated breast cancer has always been a common health problem, research focused on finding treatments suitable for the specific needs of patients with concurrent conditions is still limited. Most studies are still currently in the pre-clinical stage and mainly focus on reprogramming the glucose metabolism. More research targeting the amino acid and lipid metabolism is needed.

Curcumin, its derivatives, and their nanoformulations: Revolutionizing cancer treatment

“…46 It can inhibit cell division in the G2/M phase and reduces tumor development by modulating the miR-21 gene in HCT-116 cells. 47 Several studies observed that curcumin inhibits the JAK/STAT signaling by significantly reducing the phosphorylation of JAK2 and STAT3 levels in CRC cells 48,49 Curcumin (2 g/day) and chemotherapeutic drugs were synergistically administered in 27 CRC patients during clinical trial.…”

“…It can inhibit cell division in the G2/M phase and reduces tumor development by modulating the miR‐21 gene in HCT‐116 cells 47 . Several studies observed that curcumin inhibits the JAK/STAT signaling by significantly reducing the phosphorylation of JAK2 and STAT3 levels in CRC cells 48,49 Curcumin (2 g/day) and chemotherapeutic drugs were synergistically administered in 27 CRC patients during clinical trial. Curcumin (2 g/day) was found to be safe and tolerable, increasing patients' overall survival and response rate when administered with chemotherapeutic drugs in 27 CRC patients during clinical trial 50 …”

Atherosclerosis, Diabetes Mellitus, and Cancer: Common Epidemiology, Shared Mechanisms, and Future Management

“…Diabetes is one example where combination therapy between immunotherapy and metabolic intervention can be employed to better realize the potential of anticancer therapy. More and more evidence shows that abnormal metabolism in diabetes not only plays a key role in maintaining cancer signals of tumor occurrence and survival but also has a wider significance in regulating the anti-tumor immune response by releasing metabolites and influencing the expression of immune molecules, for instance, lactic acid and arginine [312].…”

Interlinking of diabetes mellitus and cancer: An overview

“…More research on these aspects is necessary to enhance treatment options for breast cancer in patients with diabetes. 88 In general, having advanced illness discovered in women with diabetes at the time of breast cancer diagnosis has a minor but considerable negative impact, and this may contribute to other disparities in the treatment route that may have an effect on patient outcomes. 89 The risk of breast cancer increases with diabetes.…”

“…Most preclinical research focuses on reprogramming glucose metabolism, while little attention has been paid to the metabolism of lipids and amino acids. More research on these aspects is necessary to enhance treatment options for breast cancer in patients with diabetes 88 . In general, having advanced illness discovered in women with diabetes at the time of breast cancer diagnosis has a minor but considerable negative impact, and this may contribute to other disparities in the treatment route that may have an effect on patient outcomes 89 .…”