ArticleDiscover oncology2025
MTHFD2 marks pemetrexed resistance in pulmonary adenocarcinoma with EGFR wild type.
Article in Discover oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
3 citing papers in PubMed.
- MTHFD2: a promising metabolic checkpoint for diseases.Journal of translational medicine · 2026Review
- Multi-omics analysis and experiments validate the tumor-suppressive role of mitochondrial lipid metabolism gene ACSM5 in lung adenocarcinoma and its impact on the immune microenvironment.Human genomics · 2026Article
- MTHFD2: A Retrospective and a Glance into the Future.International journal of molecular sciences · 2025Review
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Authors and funding
7 authors.
Funding
Abstract
purposeLung cancer is the leading cause of cancer-related deaths worldwide. Patients with an amplification of the MTHFD2 gene have a particularly poor prognosis. MTHFD2 signaling has been associated with migration, metastasis, and proliferation of lung cancer cells mediated through ERK signaling. Although the enzymatic activity of the MTHFD2 protein is well understood, little is known about its larger role in chemoresistance.
methodsSeventy-nine of non-small cell lung cancer (NSCLC) samples with clinical follow-up were subjected to immunohistochemical staining for MTHFD2 and sequenced using next generation sequencing (NGS) to determine EGFR status. MTHFD2 gene was knocked down in two NSCLC cell lines with wild type EGFR gene (HCC44 and H1993) where MTHFD2 signaling and chemotherapy resistance against pemetrexed were evaluated.
resultsMTHFD2 expression data revealed a strong prognosis relevance in adenocarcinoma (LUAD). Immunoblotting of cell lines showed a MTHFD2 dependent and cell type specific ERK signaling in EGFR wild type cells. MTHFD2 expression induced proliferation of NSCLC cells and their resistance against pemetrexed. Knocking down the MTHFD2 gene induced cycle arrest, however, it did not activate apoptosis signaling within HCC44 cell line.
conclusionsMTHFD2 expression is strongly associated with prognosis in LUAD patients, as well as with increased cellular proliferation and resistance to pemetrexed in LUAD patients with wild-type EGFR. These findings suggest that MTHFD2 could serve as a valuable biomarker for predicting treatment outcomes in LUAD. Further studies are needed to fully explore the clinical implications and potential combination therapies targeting MTHFD2 in LUAD.
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