Pharmacologic Inhibition of Amino Acid Metabolism

The hypothesis that selective amino acid deprivation inhibits tumor growth is also being evaluated through the pharmacologic inhibition of specific amino acid metabolism.9 Multiple drugs have been developed and are in preclinical to phase 2 studies that target specific enzymatic steps in the metabolism of amino acids such as arginine, tryptophan, serine, glycine, glutamine, and leucine, isoleucine, and valine.


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For example, several clinical trials are evaluating arginine deiminase (ADI-PEG20), which depletes arginine. A phase 3 trial of patients with advanced hepatocellular carcinoma, however, found no difference in overall survival or progression-free survival compared with placebo.10 Other trials are ongoing that are evaluating arginine deiminase in other cancer types and in combination with other therapies.11

Conclusions

In vitro and in vivo data suggest that selective amino acid deprivation may have anticancer activity; agents that inhibit select amino acid metabolism are being developed as anticancer therapy. The CAAT protocol, however, has not been formally evaluated in preclinical or clinical studies.

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Though some components of the CAAT protocol have been studied, few have shown efficacy in clinical trials. There are insufficient data to suggest that the CAAT protocol is an effective treatment for cancer.

References

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