New advances in the key mechanisms of branched-chain amino acid metabolism in tumors and research on targeted drugs

Liang Zhengyan; Gao Shouhong; Wang Zhipeng

doi:10.16689/j.cnki.cn11-9349/r.2026.04.018

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Electronic Journal of Metabolism and Nutrition of Cancer ›› 2026, Vol. 13 ›› Issue (4) : 582-588. DOI: 10.16689/j.cnki.cn11-9349/r.2026.04.018

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New advances in the key mechanisms of branched-chain amino acid metabolism in tumors and research on targeted drugs

Liang Zhengyan, Gao Shouhong, Wang Zhipeng

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Abstract

Branched-chain amino acid (BCAA) metabolism is a critical component of metabolic reprogramming in cancer. BCAA, including valine, leucine, and isoleucine, are transported into cancer cells via LAT1 and catabolized by BCAT1/2 to produce branched-chain α-keto acids, which are further metabolized by the BCKDH complex to fuel the tricarboxylic acid cycle. Dysregulated BCAA metabolism activates oncogenic signaling pathways such as mTORC1, ERK, and PI3K/Akt, thereby promoting proliferation, stemness, metastasis, and immune evasion. Notably, BCAA metabolism exhibits cancer-type-specific heterogeneity across lung, breast, colorectal, liver, pancreatic cancers, and leukemia. Emerging therapeutic strategies targeting LAT1, BCAT1, BCAT2, and BCKDH with small-molecule inhibitors (e.g., JPH203, Eupalinolide B, BT2) have shown preclinical antitumor efficacy. This review summarizes the functional heterogeneity, molecular mechanisms, and therapeutic advances of BCAA metabolism in different cancers, providing insights into metabolic targeting strategies.

Key words

Branched chain amino acids / Tumor / Branched chain amino acids transaminase / Branched-chain ketoacid / Signal pathway / Small molecule inhibitors / Research progress / Targeted therapy

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Liang Zhengyan, Gao Shouhong, Wang Zhipeng. New advances in the key mechanisms of branched-chain amino acid metabolism in tumors and research on targeted drugs[J]. Electronic Journal of Metabolism and Nutrition of Cancer. 2026, 13(4): 582-588 https://doi.org/10.16689/j.cnki.cn11-9349/r.2026.04.018

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