Metabolic pathways promote the chemical reactions of anaerobic and aerobic respiration to generate cellular energy through the breakdown of sugars. The lactic acid cycle (anaerobic) generates ATP in the absence of oxygen and the TCA cycle (aerobic) generates ATP in the presence of oxygen. In humans, the TCA cycle occurs in cellular mitochondria and is the metabolic pathway that controls carbohydrate, fat, and protein metabolism. Ultimately, these chemical processes generate cellular energy to carry out processes such as cell growth, proliferation, differentiation, and survival. 
Figure 1. Glycolysis breaks down glucose into two pyruvate molecules. In the absence of oxygen, pyruvate enters the lactic acid cycle and, via lactate dehydrogenase, produces lactic acid and 2 molecules of ATP. In the presence of oxygen, pyruvate is imported into the mitochondria and converted into acetyl-CoA. Acetyl-CoA enters the citric acid cycle (inset Box A) in order to produce the coenzymes NADH and FADH2. These coenzymes act as electron carriers to bring electrons to the electron transport chain (ETC; inset Box B), where they are used to drive the transport of protons across the inner mitochondrial membrane to generate a strong proton gradient. The influx of protons along the gradient is utilized by the ATP synthase to drive the generation of ATP by oxidative phosphorylation. The entrance of the two pyruvate molecules into the citric acid cycle and the ETC allows the generation of 32 molecules of ATP per initial glucose molecule. These metabolic processes are important for cellular metabolic regulation and contribute to healthy functioning by promoting processes such as cell growth, proliferation, differentiation, and survival.
IDH1 and IDH2 are the most frequent biomarkers that serve as inclusion criteria in therapies targeting the metabolic signaling pathway.
Biomarkers in the metabolic signaling pathway serve as inclusion eligibility criteria in 55 clinical trials, of which 50 are open and 5 are closed. The genes IDH1, IDH2, and FH on this pathway most frequently harbor alterations that are inclusion eligibility criteria for clinical trials.
Of the trials that contain alteration(s) in the metabolic signaling pathway as inclusion criteria, 2 are n/a (2 open), 18 are phase 1 (16 open), 11 are phase 1/phase 2 (10 open), 20 are phase 2 (18 open), and 4 are phase 3 (4 open) .