ArticleCell death & disease2025
PHGDH inhibition and FOXO3 modulation drives PUMA-dependent apoptosis in osteosarcoma.
Article in Cell death & disease, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
What it found
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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.
The trial behind it
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
9 citing papers in PubMed.
- Multi-Modal Analysis of Programmed Cell Death Identifies Biomarkers and Informs Prognosis in Osteosarcoma.International journal of molecular sciences · 2026Article
- The future of Forkhead box O transcription factors.The Biochemical journal · 2026Review
- PHGDH at the crossroads: metabolic plasticity, metastatic paradoxes, and therapeutic reconnaissance in cancer.Journal of biomedical science · 2026Review
- Integrated transcriptomic analysis and experimental validation identify ACADL as a mitochondrial tumor suppressor via the FOXO3a/PUMA axis in lung adenocarcinoma.European journal of medical research · 2026Article
- Metabolic-immune crosstalk in osteosarcoma: mechanisms and therapeutic opportunities.Frontiers in immunology · 2026Review
- Targeting CHD1L suppresses prostate cancer progression via the FOXO3-PUMA axis.Journal of translational medicine · 2025Article
- Targeting mitochondrial dysfunction to intervene in liver cancer.Cancer biology & medicine · 2025Review
- Osteosarcoma immunometabolism: emerging mechanisms and clinical implications.Frontiers in immunology · 2025Review
- Exploring the Causal Relationship Between Circulating miRNAs and Sepsis Through Mendelian Randomization Analysis.Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/HemostasisArticle
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
Osteosarcoma is a bone cancer that has been found to be metabolically dependent on the conversion of glucose to serine through the rate-limiting enzyme 3-phosphoglycerate dehydrogenase (PHGDH). The upregulation of PHGDH has been correlated with poor patient survival, and the inhibition of the serine synthesis pathway using targeted small-molecule inhibition of PHGDH induces a rapid metabolic adaptation that prevents cell death due to pro-survival signaling through the mammalian target of rapamycin complex 1 (mTORC1) pathway. Here, PHGDH inhibition in combination with mTORC1 signaling modulation for the treatment of osteosarcoma was evaluated. When combined with PHGDH inhibition, several non-rapalog inhibitors of mTORC1 activated Forkhead box O (FOXO) transcription factor 3 (FOXO3), a transcription factor associated with various cellular processes driving apoptosis. The activation of FOXO3 led to transcriptional activation of the pro-apoptotic gene p53 upregulated modulator of apoptosis (PUMA), inducing apoptosis when combined with PHGDH inhibition. These data suggest a path for the clinical development of PHGDH inhibitors in conjunction with mTORC1 pathway modulators in osteosarcoma.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.