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Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry
Serine synthesis pathway inhibition cooperates with dietary serine and glycine limitation for cancer therapy
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Paper Summary
Conflicts of Interest
Identified Weaknesses
Rating Explanation
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Paper Summary
Paperzilla title
Starving Cancer of Serine: A Double Whammy with Diet and Drugs!
This study reveals that inhibiting the serine synthesis pathway (SSP) using a drug called PH755, combined with a diet low in serine and glycine, can effectively curb cancer growth. This combo approach works even against tumors that resist either the diet or drug alone, highlighting its potential as a promising cancer therapy.
Possible Conflicts of Interest
One author is affiliated with Raze Therapeutics, Inc., which may have a commercial interest in the development of PHGDH inhibitors.
Identified Weaknesses
Discrepancy between in vitro and in vivo findings regarding ATF-4 response
While the in vitro results demonstrate a clear effect on the ATF-4 response and protein synthesis, the in vivo results do not show the same effect, likely due to the incomplete depletion of serine in the tumor microenvironment. This difference between in vitro and in vivo responses limits the translatability of the findings and raises questions about the true mechanism of tumor growth inhibition in the animal model.
Reliance on xenograft models
The study primarily focuses on xenograft models, which may not fully recapitulate the complexity of human tumor development and progression. The use of immunocompetent mice for toxicity assessment is valuable, but the lack of a syngeneic tumor model weakens the conclusions regarding therapeutic efficacy.
Toxicity and weight loss associated with treatment
Although the combination treatment showed efficacy, it also caused significant weight loss in mice. While the weight loss was manageable with dose adjustments, it still raises concerns about potential side effects and the therapeutic window.
Rating Explanation
This study presents strong evidence for the therapeutic potential of combining a serine/glycine restricted diet with PHGDH inhibition in cancer. The research is well-designed, employs multiple in vitro and in vivo models, and provides mechanistic insights. Despite some limitations, such as the difference in ATF-4 response between in vitro and in vivo settings and the reliance on xenograft models, the overall quality and impact of the study merit a rating of 4.
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File Information
Original Title:
Serine synthesis pathway inhibition cooperates with dietary serine and glycine limitation for cancer therapy
File Name:
s41467-020-20223-y.pdf
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File Size:
3.13 MB
Uploaded:
July 14, 2025 at 11:12 AM
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