Potential Therapeutic Targets in Energy Metabolism Pathways of Breast Cancer

Background: Mutations in proto-oncogenes and tumor suppressor genes make cancer cells proliferate indefinitely. As they possess almost all mechanisms for cell proliferation and survival like healthy cells, it is difficult to specifically target cancer cells in the body. Current treatments in most of the cases are harmful to healthy cells as well. Thus, it would be of great prudence to target specific characters of cancer cells. Since cancer cells avidly use glucose and glutamine to survive and proliferate by upregulating the relevant enzymes and their specific isoforms having important regulatory roles, it has been of great interest recently to target the energy-related metabolic pathways as part of the therapeutic interventions.

Objective: This paper summarizes the isozymes overexpressed in breast cancer, their roles of energy metabolism and cross-talks with other important signaling pathways in regulating proliferation, invasion and metastasis in breast cancer.

Method: Information has been collected from recently published literature available on Google Scholar and PubMed. Where available, in vivo results were given more importance over in vitro works.

Result: Like many other cancers, breast cancer shows increased dependence on glycolysis rather than mitochondrial respiration, the main energy source in healthy cells. Cancer cells alter the cellular energy system in a way that helps minimize level of reactive oxygen species and simultaneously produce enough macromolecules- proteins, lipids and nucleotides for cellular proliferation. The altered system enables the cells to grow, proliferate, metastasize and to develop drug resistance. Certain isozymes of metabolic enzymes are overexpressed in breast cancer and the degree of expression of these enzymes vary among subtypes.

Conclusion: A clear understanding of the variations of energy metabolism in different molecular subtypes of breast cancer would help in treating each type with a very customized, safer and efficient treatment regimen. Anti-cancer drugs or RNAi or combination of both targeting cancer cell specific isozymes of metabolic enzymes mentioned in this article could offer a great treatment modality for breast cancer.

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