Trends in Endocrinology & Metabolism: "Starve" cancer cells, the approach and challenge of amino acid depletion therapy

In the past few decades, the advancement of chemotherapy and the advent of immunotherapy and targeted therapies have significantly improved the survival rate of cancer patients.

Unlike normal cells, cancer cells can proliferate indefinitely and destroy normal tissues.

Recently, researchers from the Princess Marsima Pediatric Cancer Center of the Netherlands published a review article titled Amino Acid Depletion Therapies: Starving Cancer Cells to Death in the sub-Journal of Cell, Trends in Endocrinology & Metabolism (IF: 11.

The target of amino acid depletion therapy

Changes in the amino acid metabolism pathways of tumor cells are often driven by a variety of signaling pathways and transcription factors.

Schematic diagram of different strategies for targeting amino acid metabolism

Asparagine

So far, Asparagine (Asn) is the most successful and proven target in amino acid depletion therapy, especially in children with acute lymphoblastic leukemia.

Glutamine

Glutamine (Gln) is the most abundant free amino acid in the body.

Arginine

Arginine (Arg) is an amino acid compound that can be synthesized from glutamine (Gln) and proline (Pro).

Methionine

Methionine (Met) is one of the essential amino acids that constitute the human body and the most important methyl donor in the human body, affecting biosynthesis and metabolism.

Serine

Serine is a non-essential amino acid that depends on food intake and plays a role in fat and fatty acid metabolism and muscle growth.

Cysteine

Cysteine ​​is one of the few sulfur-containing amino acids and is essential for redox homeostasis.

Factors affecting the effect of amino acid intervention

Different intervention strategies

Although the consumption of amino acids is a potential anti-tumor strategy, in some cases, increasing the abundance of specific amino acids may have anti-tumor effects.

Tumor location

The impact of amino acid intervention on tumor development is not only related to the type of tumor, but also depends on external factors including the location of the tumor.

The effect of amino acid intervention is highly dependent on many factors

Immune surveillance

T lymphocytes are the body's "main force" against cancer cells.

Prospects and challenges of amino acid depletion therapy

When used in conjunction with different cancer therapies, the strategy of amino acid consumption can further increase the "power" of the "partner".

Drug combination of amino acid depletion therapy and chemotherapy in existing literature

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Miriam Butler， et al.