The metabolic profile of cancer cells differs significantly from that of normal cells due to their altered metabolism to support rapid proliferation, growth, and survival. This phenomenon is known as the Warburg effect or aerobic glycolysis. Understanding these differences can help develop targeted cancer therapies that exploit the unique metabolic vulnerabilities of cancer cells while sparing normal cells. Some key differences in the metabolic profile of cancer cells include:1. Enhanced glycolysis: Cancer cells preferentially use glycolysis for energy production, even in the presence of oxygen. This results in increased glucose uptake and lactate production. Targeting glycolytic enzymes or glucose transporters can potentially disrupt the energy supply of cancer cells.2. Glutamine dependence: Cancer cells have an increased dependence on glutamine, an amino acid that serves as a source of carbon and nitrogen for the synthesis of macromolecules. Inhibiting glutamine metabolism can selectively target cancer cells with minimal effects on normal cells.3. Altered lipid metabolism: Cancer cells have an increased demand for lipids to support membrane synthesis and signaling. They often upregulate fatty acid synthesis and uptake. Targeting enzymes involved in lipid metabolism can selectively impair cancer cell growth.4. Increased pentose phosphate pathway PPP activity: The PPP generates ribose-5-phosphate, a precursor for nucleotide synthesis, and NADPH, which is essential for redox homeostasis and lipid synthesis. Cancer cells often have increased PPP activity to support their rapid proliferation. Inhibiting key enzymes in the PPP can selectively target cancer cells.5. Altered mitochondrial function: Cancer cells often have altered mitochondrial function, including changes in the tricarboxylic acid TCA cycle, oxidative phosphorylation, and the electron transport chain. Targeting mitochondrial metabolism can selectively impair cancer cell survival and growth.6. Adaptation to hypoxia: Cancer cells can adapt to low oxygen conditions hypoxia by upregulating hypoxia-inducible factors HIFs that promote angiogenesis, glycolysis, and other survival pathways. Inhibiting HIFs or their downstream targets can selectively target cancer cells in hypoxic regions.By understanding these metabolic differences, researchers can develop targeted cancer therapies that exploit the unique vulnerabilities of cancer cells. Some examples of targeted therapies under investigation include inhibitors of glycolytic enzymes e.g., hexokinase, lactate dehydrogenase , glutaminase inhibitors, and fatty acid synthase inhibitors. Additionally, combining metabolic inhibitors with other targeted therapies or immunotherapies may enhance the overall effectiveness of cancer treatment.