Enhanced Radiosensitivity and Chemosensitivity of Breast Cancer Cells by 2-Deoxy-D-Glucose in Combination Therapy

Breast cancer, as the most common malignancy, is the major cause of cancer-related deaths of women worldwide

Fahimeh Aghaee

2012

Scholarcy highlights

  • Breast cancer, as the most common malignancy, is the major cause of cancer-related deaths of women worldwide
  • A number of factors contribute to these two diversified responses, which includes the extent of glucose dependence and glycolysis, energy deprivation in the form of adenosine triphosphate depletion and imbalance in the oxidative stress, levels of glucose transporters, c-Myc status, p53, and p21 status, and the levels of apoptosis regulating B-cell lymphoma family of proteins, the Bcl2/Bcl-2–associated X protein ratio
  • A great degree of heterogeneity in the 2-DG-induced modifications in radiation responses has been observed among the various human tumor cell lines that does not correlate well with the extent of decrease in the energy status, suggesting thereby that other disturbances caused by 2-DG play important roles in the modifications of cellular responses to damage caused by radiation and chemotherapeutic drugs
  • If cancer cells increase glucose metabolism to form pyruvate and nicotinamide adenine dinucleotide phosphate as a compensatory mechanism, in response to reactive oxygen species formed as byproducts of oxidative energy metabolism, inhibition of glucose metabolism would be expected to sensitize cancer cells to agents that increase levels of hydroperoxides
  • It is suggested that trastuzumab has antitumor effects in combination with glycolysis inhibitors in erythroblastosis oncogene B2-positive breast cancer by inhibiting glycolysis via downregulation of heat shock factor 1 and lactate dehydrogenase A in ErbB2-positive cancer cells, resulting in tumor growth inhibition
  • Elucidation of various mechanisms underlying radiosensitization and chemosensitization by 2-DG using established tumor cell lines will be very useful in designing effective protocols using 2-DG in cancer therapy

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