FIGURE 1.

Metabolic mechanisms of therapy induced cancer resistance. Therapy resistant cancer cells with altered metabolism can achieve resistance through a variety of mechanisms. These cells may have greater TCA cycling, leading to increased NADH and FADH₂ which feeds the ETC. To buffer ROS generated from the ETC, lipids, and other cellular reactions, therapy resistant cells may upregulate enzymes that consume ROS. GSH generated from glutamine can be a key enzyme to buffer ROS. Glucose can generate pyruvate through glycolysis, which can then enter the mitochondria and generate acetyl-CoA for the TCA cycle. Alternatively, glucose may feed the PPP. Similarly, fatty acids can be generated through FAS, forming LDs, or entering directly into the mitochondria to undergo FAO, providing acetyl-CoA for the TCA cycle. Glutamine can feed nucleotide synthesis, amino acid synthesis, or into the mitochondria and the TCA cycle as glutamate. Group numbers indicate the metabolic dependency of studies found in this paper, which can be found in Table 1.