Seminars

Metabolism is an essential process to acquire necessary nutrients from outside of cells and utilize them in their biomass to maintain cell viability. In a tumor microenvironment that has limited nutrients and oxygen, nutrient availability and nutritional stresses often rewire metabolic pathways of cancer cells. Hence, cancer cells exhibit distinct metabolic phenotypes to support their survival and proliferation states in tumor microenvironment. The most common metabolic phenotypic changes in cancer cells are increased glucose uptake for aerobic glycolysis and lactate production even in the presence of oxygen. In response to the metabolic stress or oncogenic signals, cancer cells also utilize alternative carbon and energy sources such as fatty acids and amino acids, including glutamine, using micropinocytosis to fulfill increased energy demands. Due to the distinct cancer metabolism, blocking primary metabolic pathways of cancer cells generates a cancer vulnerability by effectively reducing proliferation of cancer cells or inhibiting survival of cancer cells. Currently, several drugs targeting altered and activated metabolic pathways in cancer cells have been approved, or are under current clinical trials as a potential cancer treatment. However, inhibition of particular metabolic pathways can be ineffective or less effective, because cancer cells have the metabolic flexibility to use different substrates or alternative metabolic pathways to adapt various resources for their survival. Thus rewiring their metabolism is crucial to make cancer cells more targetable and susceptible. For this purpose, it is necessary to understand cancer metabolism to achieve a more effective treatment, as well as, to identify accurate prognostic and predictive biomarkers for cancer patients. Recent studies including ours identified a new functional role of BACH1 in cancer metabolism regulation demonstrating that BACH1 works as a metabolic driver in response to the intracellular and extracellular signals in breast and lung cancer cells. Our findings highlight recent advances in understanding of the essential role of BACH1 on cancer metabolism and its potential as a therapeutic target for cancer therapy.