A nanoparticle-delivered peptide that blocks cancer cells' ability to produce lipids shrank tumors in mice and worked even better when combined with semaglutide.
Previously 'untargetable'SREBP was considered undruggable until this peptide demonstrated effective inhibition of its activation pathway
What the researchers found
A peptide mimicking the Insig1/2 loop 1 region blocked the interaction between PCK1 and Insig1/2, shutting down the SREBP1 pathway that cancer cells use to produce the lipids they need to grow. When delivered intravenously in liposomal nanoparticles, the peptide suppressed tumor growth and extended survival in mice without apparent side effects. Combining the peptide with either lenvatinib (a cancer drug) or semaglutide (an anti-obesity drug) produced additive anti-tumor effects. This is the first demonstration that SREBP — previously considered 'untargetable' — can be inhibited with a peptide therapeutic.
Why it matters
Cancer cells produce far more fat molecules than normal cells, fueling their rapid growth. The SREBP pathway controlling this fat production has been considered a promising but 'undruggable' cancer target. This study shows a peptide can hit it effectively, opening a new class of cancer therapy. The finding that semaglutide (a GLP-1 weight loss drug) has additive anti-tumor effects when combined with the peptide is particularly striking, connecting obesity treatment and cancer therapy.
How the study worked
The researchers designed a peptide replicating the amino acid sequence of the Insig1/2 loop 1 region and tested it in tumor cell lines to measure effects on SREBP1 nuclear accumulation, lipid gene expression, lipid accumulation, and cell proliferation. For in vivo testing, they encapsulated the peptide in engineered liposomal nanoparticles (LNPs) and administered them intravenously to tumor-bearing mice, measuring tumor growth and survival. Combination experiments tested the peptide with lenvatinib and semaglutide.
What this study cannot tell us
This is a preclinical study in cell lines and mouse models — human safety and efficacy are unknown. The LNP delivery system, while effective in mice, would need significant optimization for human use. Long-term effects of blocking SREBP-mediated lipogenesis on normal cells that also require fat synthesis are not addressed. The mechanisms behind semaglutide's additive effect were not fully explored.
How to read the evidence
This is a preclinical study with rigorous in vitro mechanistic work and in vivo tumor models in mice. Published in Advanced Science, it demonstrates proof-of-concept but has not been tested in humans.
When this study was published
Published in 2025, this is cutting-edge research at the intersection of peptide therapeutics, nanotechnology, and cancer metabolism. It has not yet been replicated or advanced to clinical trials.
The bigger picture
Tumor metabolism is one of the hottest frontiers in cancer research, and this study connects it directly to the peptide therapeutics world. The finding that semaglutide enhances the peptide's anti-tumor effect is particularly significant given the massive patient population now using GLP-1 drugs — it raises the tantalizing possibility that weight loss drugs may have cancer-related benefits beyond reducing obesity-associated cancer risk.
Questions still open
- How does semaglutide produce additive anti-tumor effects — through metabolic changes, direct anti-proliferative effects, or both?
- Can the LNP delivery system be optimized to target specific tumor types while sparing normal tissues that depend on SREBP-mediated lipogenesis?
- Would this peptide approach be effective against cancers known to be particularly lipid-dependent, such as prostate and ovarian cancer?
Common questions
Why do cancer cells need so much fat?
Why would a weight loss drug like semaglutide help fight cancer?
Read the original research
Inhibition of Tumor Lipogenesis and Growth by Peptide-Based Targeting of SREBP Activation.
Advanced science (Weinheim, Baden-Wurttemberg, Germany), 12(45), e08111
Citation
Luo, Shudi; Yang, Huang; Jiang, Xiaoming; Wang, Zheng; He, Xuxiao; Meng, Ying; Li, Shan; Li, Min; Xu, Daqian; Mao, Zhengwei; Lu, Zhimin. (2025). Inhibition of Tumor Lipogenesis and Growth by Peptide-Based Targeting of SREBP Activation.. Advanced science (Weinheim, Baden-Wurttemberg, Germany), 12(45), e08111. https://doi.org/10.1002/advs.202508111