Title:Potential Therapeutic Targets in Energy Metabolism Pathways of Breast Cancer
VOLUME: 17 ISSUE: 8
Author(s):Rowshan Ara Islam, Sazzad Hossain and Ezharul Hoque Chowdhury*
Affiliation:Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Jalan Lagoon Selatan, Bandar Sunway, 47500 Subang Jaya, Selangor, InMed Pharmaceuticals, Vancouver, V6C 1T2, Jeffrey Cheah School of Medicine and Health Sciences, Faculty of Medicine, Nursing and Health Sciences, MONASH University
Keywords:Breast cancer, glycolysis, TCA cycle, pentose phosphate pathway, glutaminolysis, proto-oncogenes.
Abstract: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.
