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Targeting Amino Acid Metabolic Vulnerabilities in Myeloid Malignancies
Livingstone Fultang1, Luciana Gneo1, Carmela De Santo1
1Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom.
Abstract:
Tumor cells require a higher supply of nutrients for growth and proliferation than normal cells. It is well established that metabolic reprograming in cancers for increased nutrient supply exposes a host of targetable vulnerabilities. In this article we review the documented changes in expression patterns of amino acid metabolic enzymes and transporters in myeloid malignancies and the growing list of small molecules and therapeutic strategies used to disrupt amino acid metabolic circuits within the cell. Pharmacological inhibition of amino acid metabolism is effective in inducing cell death in leukemic stem cells and primary blasts, as well as in reducing tumor burden in in vivo murine models of human disease. Thus targeting amino acid metabolism provides a host of potential translational opportunities for exploitation to improve the outcomes for patients with myeloid malignancies.
Insights
Cancer cells need more nutrients, offering vulnerabilities. Targeting amino acid metabolism in myeloid malignancies shows promise for effective cancer cell death and reduced tumor burden in preclinical models.
Area of Science:
- Oncology
- Cancer Metabolism
- Hematology
Background:
- Tumor cells exhibit altered nutrient requirements for growth and proliferation.
- Metabolic reprogramming in cancer creates vulnerabilities targeting nutrient supply pathways.
- Amino acid metabolism is a critical pathway dysregulated in various cancers.
Purpose of the Study:
- To review documented changes in amino acid metabolism in myeloid malignancies.
- To summarize therapeutic strategies targeting amino acid metabolic circuits.
- To highlight translational opportunities for myeloid malignancy treatment.
Main Methods:
- Review of literature on amino acid metabolic enzymes and transporters in myeloid malignancies.
- Analysis of small molecules and therapeutic strategies targeting cancer metabolism.
- Evaluation of preclinical data from murine models.
Main Results:
- Documented alterations in expression patterns of amino acid metabolic enzymes and transporters in myeloid malignancies.
- Identification of numerous small molecules and therapeutic strategies for disrupting amino acid metabolism.
- Demonstrated efficacy of pharmacological inhibition in inducing leukemic cell death and reducing tumor burden in vivo.
Conclusions:
- Targeting amino acid metabolism presents significant translational potential for myeloid malignancies.
- Inhibition of amino acid metabolism is effective against leukemic stem cells and primary blasts.
- Exploiting metabolic vulnerabilities offers a promising avenue for improving patient outcomes.
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