What does this research mean for the field?

PHGDH drives 5-Fluorouracil resistance in colorectal cancer through non-enzymatic upregulation of the Hedgehog signaling pathway, and combined treatment with 5-FU and Hedgehog inhibitors can overcome this resistance. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

To investigate the non-enzymatic mechanisms by which phosphoglycerate dehydrogenase (PHGDH) promotes resistance to 5-fluorouracil (5-FU) in colorectal cancer.

July 10, 2025Journal of Experimental & Clinical Cancer ResearchOpen Access

PHGDH drives 5-FU chemoresistance in colorectal cancer through the Hedgehog signaling

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To investigate the non-enzymatic mechanisms by which phosphoglycerate dehydrogenase (PHGDH) promotes resistance to 5-fluorouracil (5-FU) in colorectal cancer.
Modulated PHGDH expression through gene silencing and overexpression in human colorectal cancer cell lines, validating targets in 5-FU-resistant cells, patient tissue specimens, and 3D organoids.
Performed transcriptomic profiling on wild-type and PHGDH-silenced colorectal cancer cells to identify downstream pathways driving resistance.
Evaluated the efficacy of combining 5-FU with Hedgehog pathway inhibitors using in vitro cell viability assays and an in vivo colorectal cancer xenograft mouse model.
PHGDH expression correlated with therapeutic response in retrospective colorectal cancer patient cohorts, with gene silencing directly restoring 5-FU sensitivity in cancer cells.
Transcriptomic analysis of PHGDH-silenced colorectal cancer cell lines revealed significant downregulation of the Hedgehog signaling pathway.
Combined treatment using 5-FU and Hedgehog pathway inhibitors significantly suppressed cancer cell survival and hindered tumor growth in colorectal cancer xenografts.

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Implication

Preclinical study reveals that PHGDH drives 5-FU chemoresistance via Hedgehog signaling in colorectal cancer models, indicating that dual inhibition restores chemosensitivity.

Cite This Study

Mancini et al. (2025) studied this question.

synapsesocial.com/papers/6a7294ae5671bbf00bc317c3 https://doi.org/10.1186/s13046-025-03447-y

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Implication

Preclinical study reveals that PHGDH drives 5-FU chemoresistance via Hedgehog signaling in colorectal cancer models, indicating that dual inhibition restores chemosensitivity.

PHGDH drives 5-FU chemoresistance in colorectal cancer through the Hedgehog signaling

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Discussion

Implication

Cite This Study

PHGDH drives 5-FU chemoresistance in colorectal cancer through the Hedgehog signaling

Key Points

Discussion

Implication

Cite This Study

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