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The vulnerability of cancer cells to nutrient deprivation and their dependency on specific metabolites

Summary #

Cancer cells are known for their rapid and uncontrollable growth, which requires a continuous supply of nutrients to fuel their proliferation. Recent studies have shown that these cells are particularly vulnerable to nutrient deprivation and have a unique dependency on specific metabolites. This blog post will delve into the vulnerability of cancer cells to nutrient deprivation and their dependency on specific metabolites, as well as explore potential therapeutic strategies targeting these vulnerabilities.

In Depth #

Cancer cells have a high demand for nutrients to support their rapid growth and division. To meet these demands, they often hijack normal cellular processes and develop unique metabolic dependencies. This characteristic can be exploited as a potential therapeutic strategy, by depriving cancer cells of the nutrients they need to survive and grow.

One key nutrient that cancer cells depend on is glucose. Many cancer cells exhibit a phenomenon known as the Warburg effect, where they preferentially use glycolysis (the breakdown of glucose) to generate energy, even in the presence of oxygen. This is in contrast to normal cells, which primarily use oxidative phosphorylation when oxygen is present. This increased reliance on glucose makes cancer cells more vulnerable to glucose deprivation.

Another nutrient that cancer cells are highly dependent on is the amino acid glutamine. Glutamine is the most abundant amino acid in the body and plays a crucial role in various cellular processes, including energy production, protein synthesis, and nucleotide synthesis. Cancer cells often exhibit an increased rate of glutamine uptake and metabolism, which is necessary for their survival and growth. Targeting glutamine metabolism is an emerging therapeutic strategy in cancer treatment.

In addition to their vulnerability to nutrient deprivation, cancer cells also exhibit a unique dependency on specific metabolites. One such example is the dependency of certain cancer cells on the enzyme isocitrate dehydrogenase (IDH). Mutations in the IDH gene have been found in various cancer types, including gliomas and acute myeloid leukemia. These mutations result in the production of an oncometabolite called 2-hydroxyglutarate (2-HG), which promotes cancer cell growth and survival. Targeting IDH mutations with small molecule inhibitors has shown promising results in preclinical and clinical studies.

Another example of cancer cell dependency on specific metabolites is the reliance on one-carbon metabolism. One-carbon metabolism is a cellular process that generates essential building blocks for nucleotide synthesis, amino acid homeostasis, and methylation reactions. Cancer cells often exhibit an increased demand for one-carbon units, making them more sensitive to the inhibition of one-carbon metabolism enzymes.

These vulnerabilities of cancer cells to nutrient deprivation and their dependency on specific metabolites present promising therapeutic opportunities. By targeting these metabolic dependencies, researchers hope to develop more effective and selective treatments for various cancer types.

Further Reading #

  1. Vander Heiden, M. G., & DeBerardinis, R. J. (2017). Understanding the Intersections between Metabolism and Cancer Biology. Cell, 168(4), 657-669. Link
  2. Pavlova, N. N., & Thompson, C. B. (2016). The Emerging Hallmarks of Cancer Metabolism. Cell Metabolism, 23(1), 27-47. Link
  3. DeBerardinis, R. J., & Chandel, N. S. (2016). Fundamentals of cancer metabolism. Science Advances, 2(5), e1600200. Link
  4. Altman, B. J., Stine, Z. E., & Dang, C. V. (2016). From Krebs to clinic: glutamine metabolism to cancer therapy. Nature Reviews Cancer, 16(10), 619-634. Link