Combination therapy targeting cancer metabolism.
Cancer cells undergo significant metabolic adaptation. Cellular transformation enhances both glycolysis and mitochondrial respiration efficiency through the induction of HIF-1α and HIF-2α. In this process, energy production and synthesis of macromolecules are maximized with minimal ROS accumulation. Furthermore, a series of antioxidant enzymes are induced to mitigate the damaging effects of ROS. Examination of these metabolic changes provides rationale for a synergistic approach to combination anti-cancer therapy; targeted inhibition of HIF and inhibition of cellular defenses against oxidative stress.
Division of Hematology/Oncology, Department of Internal Medicine, University of Florida Shands Cancer Center, University of Florida, Gainesville, FL 32610-0278, United States.
Justin B
JB
Wenger
Sang Y
SY
Chun
Duyen T
DT
Dang
Hendrik
H
Luesch
Long H
LH
Dang
D000970:Antineoplastic Agents / Q000494:pharmacology; D000975:Antioxidants / Q000378:metabolism; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism; D006019:Glycolysis; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D046911:Macromolecular Substances; D008928:Mitochondria / Q000378:metabolism; D008954:Models, Biological; D009369:Neoplasms / Q000378:metabolism*; D018384:Oxidative Stress; D017382:Reactive Oxygen Species; D000099162:Endothelial PAS Domain-Containing Protein 1
D000970:Antineoplastic Agents; D000975:Antioxidants; D051792:Basic Helix-Loop-Helix Proteins; D005947:Glucose; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D046911:Macromolecular Substances; D017382:Reactive Oxygen Species; D000099162:Endothelial PAS Domain-Containing Protein 1; C497442:HIF1A protein, human