Oncometabolism

Study of metabolic changes in cancer cells

Classification
External resources

Oncometabolism is the study of the metabolic changes that occur in cancer cells. These changes are crucial for understanding how cancer cells grow, survive, and proliferate. The field of oncometabolism explores how cancer cells alter their metabolism to support rapid growth and how these changes can be targeted for cancer therapy.

Overview

Cancer cells exhibit altered metabolism compared to normal cells. One of the most well-known metabolic alterations in cancer is the Warburg effect, named after the German biochemist Otto Warburg.

Otto Warburg, who first described the Warburg effect

The Warburg Effect

The Warburg effect describes the preference of cancer cells to produce energy through glycolysis followed by lactic acid fermentation in the cytoplasm, rather than by a comparatively energy-efficient oxidative phosphorylation in the mitochondria. This occurs even in the presence of sufficient oxygen, a phenomenon known as "aerobic glycolysis."

Diagram illustrating the Warburg effect

This metabolic reprogramming allows cancer cells to generate the necessary building blocks for rapid cell division and growth. The increased uptake of glucose and the production of lactate are hallmarks of the Warburg effect.

Key Metabolic Pathways in Cancer

Several metabolic pathways are altered in cancer cells:

Glycolysis

Cancer cells often upregulate glycolysis to meet their increased energy demands. This is facilitated by the overexpression of glycolytic enzymes and transporters.

Tricarboxylic Acid Cycle

Alterations in the tricarboxylic acid cycle (TCA cycle) are also observed in cancer cells. Mutations in enzymes such as isocitrate dehydrogenase (IDH) can lead to the production of oncometabolites that promote tumorigenesis.

Structure of isocitrate dehydrogenase, an enzyme involved in the TCA cycle

Lipid Metabolism

Cancer cells often exhibit increased lipid synthesis and uptake, which are essential for membrane biosynthesis and energy storage.

Amino Acid Metabolism

Alterations in amino acid metabolism, such as increased glutamine uptake and metabolism, are also common in cancer cells. Glutamine serves as a carbon and nitrogen source for biosynthetic processes.

Oncometabolites

Oncometabolites are metabolites that accumulate in cancer cells due to metabolic reprogramming and contribute to cancer progression. Examples include 2-hydroxyglutarate, succinate, and fumarate.

Exosomes and Metabolic Communication

Cancer cells can influence the metabolism of surrounding cells through the release of exosomes, which are small vesicles that carry proteins, lipids, and nucleic acids.

Exosomes play a role in intercellular communication

Therapeutic Implications

Understanding the metabolic alterations in cancer cells has led to the development of targeted therapies. Inhibitors of glycolysis, lipid metabolism, and specific oncometabolites are being explored as potential cancer treatments.

Related pages

• Cancer metabolism
• Metabolic pathway
• Tumor microenvironment