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Exploring the potential of asparagine restriction in solid cancer treatment: recent discoveries, therapeutic implications, and challenges

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Abstract

Asparagine is a non-essential amino acid crucial for protein biosynthesis and function, and therefore cell maintenance and growth. Furthermore, this amino acid has an important role in regulating several metabolic pathways, such as tricarboxylic acid cycle and the urea cycle. When compared to normal cells, tumor cells typically present a higher demand for asparagine, making it a compelling target for therapy. In this review article, we investigate different facets of asparagine bioavailability intricate role in malignant tumors raised from solid organs. We take a comprehensive look at asparagine synthetase expression and regulation in cancer, including the impact on tumor growth and metastasis. Moreover, we explore asparagine depletion through L-asparaginase as a potential therapeutic method for aggressive solid tumors, approaching different formulations of the enzyme and combinatory therapies. In summary, here we delve into studies about endogenous and exogenous asparagine availability in solid cancers, analyzing therapeutic implications and future challenges.

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The authors would like to thank the São Paulo Research Foundation (FAPESP), grant numbers 2022/02456-0, 2023/07417-6, 2022/02076-3. This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Brazil (CAPES), Finance Code 001. G.M. received a Productivity Fellowship from the Brazilian National Council of Technological and Scientific Development (CNPq 306060/2022-1).

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Author notes

  1. William Henry Roldán and Gisele Monteiro have contributed equally to this work.

Authors and Affiliations

  1. Departamento de Tecnologia Bioquímico-Farmacêutica, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, São Paulo, Brazil

    Marina Gabriel Fontes, Carolina Silva, William Henry Roldán & Gisele Monteiro

Authors
  1. Marina Gabriel Fontes
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  2. Carolina Silva
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  3. William Henry Roldán
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  4. Gisele Monteiro
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Contributions

GM and MGF conceived the subject of the review. MGF, CS and WHR performed the writing and structure of the text. MGF and WHR designed the figures. CS constructed the table. All authors revised, edited and approved the final version of the manuscript, as well as its submission. GM provided financial support.

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Correspondence to Gisele Monteiro.

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Fontes, M.G., Silva, C., Roldán, W.H. et al. Exploring the potential of asparagine restriction in solid cancer treatment: recent discoveries, therapeutic implications, and challenges. Med Oncol 41, 176 (2024). https://doi.org/10.1007/s12032-024-02424-3

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