Targeting metabolism in breast cancer: How far we can go?

Abstract

receptor-2 targeted therapy, marked a new era of breast cancer treatment. However, except for chemotherapy, an efficient drug treatment to improve the overall survival of breast cancer patients is still lacking for triple negative breast cancer. Furthermore, a certain proportion of breast cancer patients present with resistance to drug therapy, making it much more difficult to control the deterioration of the disease. Recently, altered energy metabolism has become one of the hallmarks of cancer, including breast cancer, and it may be linked to drug resistance. Targeting cellular metabolism is becoming a promising strategy to overcome drug resistance in cancer therapy. This review discusses metabolic reprogramming in breast cancer and the possible complex mechanism of modulation. We also summarize the recent advances in metabolic therapy targeted glycolysis, glutaminolysis and fatty acids synthesis in breast cancer. Core tip: Breast cancer cells display distinct metabolic characteristics according to different molecular phe notypes. There may be crosstalk with the estrogen receptor and human epidermal growth factor receptor2 signal pathways in the metabolic regulation in breast cancer cells that make it more complex to evaluate the efficiency of an antimetabolic drug. On the other hand, the research on target metabolism in breast cancer will also largely help us to understand the complicated mechanism by which an antimetabolic drug impro ves the efficacy of cancer therapy or overcomes drug resistance. AbstractAdjuvant therapies for breast cancer have achieved great success in recent years and early breast cancer is now a curable or chronic disease. Targeted therapies, including endocrine therapy and human epidermal growth factor MINIREVIEWS 122February 10, 2016|Volume 7|Issue 1|

Association of long-chain acyl-coenzyme A synthetase 5 expression in human breast cancer by estrogen receptor status and its clinical significance

“…These lipid metabolites are associated with cell proliferation, cellular membrane synthesis and signaling molecules (4)(5)(6). Some of the dysregulated metabolic enzymes, such as the glucose transporter 1 (GLUT1), hexokinase 2, lactate dehydrogenase A, glutaminase and fatty acid synthase have been demonstrated to be novel therapeutic targets of cancers (7). The metabolomics in serum or plasma will be novel diagnostic approach in clinic (8).…”

“…Most breast cells acquire fatty acids from circulation system. However, breast cancer cells synthesize fatty acids for structured lipid synthesis (7). Fatty acid synthase (FAS) is an important enzyme in lipid synthesis pathway.…”

Metabolomic profiling of breast tumors using ductal fluid

“…In a recent study, Willmann et al (39), used metabolomic profiling to sub-classify different breast cancer cell lines and differentiate not only between them, but also between the cancer cell lines and a non-cancer breast epithelial cell line as well. Research has shown that elevated glycine and lactate indicate increased metabolic changes due to rapid growth of cancer cells, and hence poorer prognosis (5). …”

“…receptors), microenvironment (i.e. hypoxia), and glucose metabolism, and how the downstream expression of metabolites can be used for both early detection of breast cancer as well as targeted drug therapies (5–7). …”

Relationship between level of HbA1C and breast cancer

“…According to a review completed by Long and colleagues [19], many studies have shown dysregulation in cellular metabolism may associate with resistance to cancer treatment drugs. Various factors, including insulin, insulin-like growth factor (IGF), and inflammatory cytokines, may link diabetes to breast cancer mortality.…”