Fig. 2: Chemotherapy drugs are taken up by cancer cells, causing stress and nutrient starvation.
From: The metabolic flexibility of quiescent CSC: implications for chemotherapy resistance
Through the pentose phosphate pathway, glucose can indirectly produce NADPH, which confronts excessive intracellular ROS to maintain CSC in the quiescent state. Second, when nutrients in the TME are in short, nutrients excluding glucose are decomposed and go through OXPHOS to effectively produce ATP to sustain basic biological demand. Third, glutathione also can be synthesized from glutamine (an important and rich non-essential amino acid) and participate in the self-defense mechanism in response to excessive ROS and reduce its related adverse outcomes. Meanwhile, the intermediates in glycolysis, pyruvate, and lactate further can abnormally activate ALDH, initiating or strengthening CSC stemness.
