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  4. Vol 7, Issue 1, 2026

Tumor metabolic reprogramming driven by ARID1A deficiency and synthetic lethal mechanism

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DOI: 10.23977/medsc.2026.070109 | Downloads: 0 | Views: 57

Author(s)

Xinhong Chen 1, Yongbin Chi 2

Affiliation(s)

1 School of Gongli Hospital Medical Technology, University of Shanghai for Science and Technology, Shanghai, 200093, China
2 Shanghai Health Commission Key Lab of Artificial Intelligence (AI)-Based Management of Inflammation and Chronic Diseases, Department of Central Laboratory, Gongli Hospital of Shanghai Pudong New Area, 219 Miao Pu Road, Shanghai, 200135, China

Corresponding Author

Yongbin Chi

ABSTRACT

ARID1A, a core subunit of the SWI/SNF chromatin remodeling complex, is frequently inactivated across diverse cancers. This review synthesizes current understanding of how ARID1A deficiency serves as a pivotal epigenetic driver, orchestrating extensive metabolic reprogramming and reshaping the tumor immune microenvironment (TIME). Acting as an epigenetic hub, loss of ARID1A alters chromatin accessibility, leading to transcriptional dysregulation of key metabolic enzymes. This drives cancer-type-specific rewiring of core pathways including glucose, amino acid, lipid, and nucleotide metabolism. Crucially, these metabolic alterations extend beyond fueling tumor proliferation; they actively sculpt an immunosuppressive TIME through mechanisms such as nutrient competition, oxidative stress modulation, and the production of specific metabolites. This creates a dual vulnerability: a dependence on the reprogrammed metabolic state for survival and a disrupted immune landscape. Consequently, ARID1A deficiency exposes unique, targetable "synthetic lethal" weaknesses. We detail promising therapeutic strategies that exploit these vulnerabilities by targeting the reprogrammed metabolism (e.g., using GLS1, FASN, or DHODH inhibitors) or its immunomodulatory consequences, often in combination with immunotherapy. Despite significant preclinical progress, challenges remain, including understanding the heterogeneity of metabolic responses across cancer types and identifying validated biomarkers for patient stratification. Interdisciplinary efforts to decipher the precise mechanisms of this epigenetic-metabolic-immune crosstalk and to advance combination therapies into the clinic are essential for realizing the promise of precision medicine for ARID1A-deficient tumors.

KEYWORDS

ARID1A, Metabolism, Synthetic lethal

CITE THIS PAPER

Xinhong Chen, Yongbin Chi. Tumor metabolic reprogramming driven by ARID1A deficiency and synthetic lethal mechanism. MEDS Clinical Medicine (2026). Vol. 7, No.1, 76-99. DOI: http://dx.doi.org/10.23977/medsc.2026.070109.

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