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Review
. 2025 Nov:221:108003.
doi: 10.1016/j.phrs.2025.108003. Epub 2025 Oct 19.

Amino acid sensing in cancer

Zihao Lin  1 , Lihong He  1 , Jiawei Wang  1 , Hanjia Zhang  1 , Shicheng Yao  1 , Jingpeng Guo  1 , Xiaozhen Zhang  1 , Tingbo Liang  2 , Xueli Bai  3
Affiliations
Free article
Review

Amino acid sensing in cancer

Zihao Lin et al. Pharmacol Res. 2025 Nov.
Free article

Abstract

Tumour progression is accompanied by metabolic reprogramming, enabling adaptation to the nutrient-deprived microenvironment. Amino acids, as key metabolic substrates, play a central role in metabolic reprogramming. Beyond their conventional metabolic roles, amino acids function as signalling molecules, activating specific (e.g., BAG2, RBM39, HDAC6, and NMDA receptor) or promiscuous (e.g., GCN2, mTORC1) sensor proteins and subsequently promoting tumour cell proliferation and survival through oncogenic signalling pathways or epigenetic modifications. This review aims to summarise the non-metabolic functions of amino acids, particularly focusing on their sensor-mediated cross-talk, to utilise their potential as novel therapeutic targets.

Keywords: Amino acid metabolism; Amino acid sensors; Cancer progression; Cancer therapy; mTORC1.

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Conflict of interest statement

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.