Amino Acid Depletion Therapies: Starving Cancer Cells to Death

Miriam Butler; Laurens T van der Meer; Frank N van Leeuwen

doi:10.1016/j.tem.2021.03.003

Amino Acid Depletion Therapies: Starving Cancer Cells to Death

Trends Endocrinol Metab. 2021 Jun;32(6):367-381. doi: 10.1016/j.tem.2021.03.003. Epub 2021 Mar 29.

Authors

Miriam Butler¹, Laurens T van der Meer², Frank N van Leeuwen³

Affiliations

¹ Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands; Laboratory of Pediatric Oncology, Radboud Institute for Molecular Life Sciences, Radboud university medical center, Nijmegen, The Netherlands.
² Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.
³ Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands. Electronic address: F.N.vanLeeuwen@prinsesmaximacentrum.nl.

PMID: 33795176
DOI: 10.1016/j.tem.2021.03.003

Abstract

Targeting tumor cell metabolism is an attractive form of therapy, as it may enhance treatment response in therapy resistant cancers as well as mitigate treatment-related toxicities by reducing the need for genotoxic agents. To meet their increased demand for biomass accumulation and energy production and to maintain redox homeostasis, tumor cells undergo profound changes in their metabolism. In addition to the diversion of glucose metabolism, this is achieved by upregulation of amino acid metabolism. Interfering with amino acid availability can be selectively lethal to tumor cells and has proven to be a cancer specific Achilles' heel. Here we review the biology behind such cancer specific amino acid dependencies and discuss how these vulnerabilities can be exploited to improve cancer therapies.

Keywords: amino acid depletion therapy; amino acid metabolism; cancer; tumor metabolism.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Amino Acids* / metabolism
Humans
Neoplasms* / therapy
Oxidation-Reduction

Substances

Amino Acids