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Background <p>MTHFD2, a critical enzyme in one-carbon metabolism, regulates cellular growth, redox balance, and energy homeostasis. Aberrant MTHFD2 expression has been implicated in the pathogenesis and progression of various diseases. MTHFD2 is a promising therapeutic target, however, its roles in diseases and upstream and downstream regulatory mechanisms have not been clarified.</p> Methods <p>This study reviewed literature from databases such as PubMed and Google Scholar, using keywords “MTHFD2”, aiming to summarize current research on the functions and mechanisms of MTHFD2 on diseases and provide theoretical support for future investigation of related therapeutic strategies.</p> Results <p>High expression of MTHFD2 promotes cancer progression and MTHFD2 can be used as a sensitization target in cancer treatment. MTHFD2 influences tumor microenvironment through disturbing immune cell infiltration and immune checkpoints expression. Aberrant MTHFD2 expression can also participate in other diseases. Consequently, a range of MTHFD2 inhibitors has been developed, advancing to both preclinical and clinical evaluations.</p> Conclusions <p>This review examines the multifaceted roles of MTHFD2 in cancer biology and other pathological conditions, describing its influence on the tumor microenvironment and relevance in immunotherapeutic applications. Structural strategies for MTHFD2 inhibitor development are explored, alongside challenges and opportunities for leveraging MTHFD2 as a diagnostic, therapeutic, and prognostic target in disease management.</p>

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MTHFD2: a promising metabolic checkpoint for diseases

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年4月29日

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  • Xiang Wang,
  • Renhao Ou,
  • Yana Xu,
  • Guowan Zheng,
  • Haifeng Xu,
  • Ying Luo,
  • Yunzhao Chen,
  • Xinxin Ren

摘要

Background

MTHFD2, a critical enzyme in one-carbon metabolism, regulates cellular growth, redox balance, and energy homeostasis. Aberrant MTHFD2 expression has been implicated in the pathogenesis and progression of various diseases. MTHFD2 is a promising therapeutic target, however, its roles in diseases and upstream and downstream regulatory mechanisms have not been clarified.

Methods

This study reviewed literature from databases such as PubMed and Google Scholar, using keywords “MTHFD2”, aiming to summarize current research on the functions and mechanisms of MTHFD2 on diseases and provide theoretical support for future investigation of related therapeutic strategies.

Results

High expression of MTHFD2 promotes cancer progression and MTHFD2 can be used as a sensitization target in cancer treatment. MTHFD2 influences tumor microenvironment through disturbing immune cell infiltration and immune checkpoints expression. Aberrant MTHFD2 expression can also participate in other diseases. Consequently, a range of MTHFD2 inhibitors has been developed, advancing to both preclinical and clinical evaluations.

Conclusions

This review examines the multifaceted roles of MTHFD2 in cancer biology and other pathological conditions, describing its influence on the tumor microenvironment and relevance in immunotherapeutic applications. Structural strategies for MTHFD2 inhibitor development are explored, alongside challenges and opportunities for leveraging MTHFD2 as a diagnostic, therapeutic, and prognostic target in disease management.