Cancer cells experience an increase in oxidative stress. Excessive accumulation of oxidative stress is harmful to cancer cells. The pentose phosphate pathway (PPP) is a major biochemical pathway that generates antioxidant NADPH. The study demonstrates the important roles of a pentose phosphate pathway (PPP) enzyme, transketolase (TKT), in redox homeostasis in cancer development.
Authors show that TKT is required for cancer growth because of its ability to affect the production of NAPDH to counteract oxidative stress. Authors highlight the clinical relevance of TKT expression in cancers.
They also show that TKT overexpression in cancer cells is a response of Nuclear Factor, Erythroid 2-Like 2 (NRF2) activation, a sensor to cellular oxidative stress. TKT locates at an important position that connects PPP with glycolysis to affect production of antioxidant NADPH.
The preclinical study shows that targeting TKT leads to elevation of oxidative stress, making cancer cells more vulnerable to therapeutic treatment, such as Sorafenib. Using TKT as an example, this study suggests that targeting enzymes for antioxidant production represents a direction for cancer treatment.