Evidence map›Paper›PMID 42373728›Full record

ArticleNPJ precision oncology2026

GLP-1 receptor agonist targets an AMPKα1-HIF1α-PFKFB3 metabolic vulnerability and enhances Lenvatinib response in hepatocellular carcinoma.

Takayuki Noma, Yuan Li, Yuma Wada, Yuji Morine, Tetsuya Ikemoto, Yu Saito, Mitsuo Shimada, Ajay Goel

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in NPJ precision oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0cells of the map it votes in
0citing papers in PubMed
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1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Takayuki NomaDepartment of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute of City of Hope, Biomedical Research Center, Monrovia, California, USA.
Yuan LiDepartment of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute of City of Hope, Biomedical Research Center, Monrovia, California, USA.
Yuma WadaDepartment of Surgery, Tokushima University, Tokushima, Japan.
Yuji MorineDepartment of Surgery, Tokushima University, Tokushima, Japan.
Tetsuya IkemotoDepartment of Surgery, Tokushima University, Tokushima, Japan.
Yu SaitoDepartment of Surgery, Tokushima University, Tokushima, Japan.
Mitsuo ShimadaDepartment of Surgery, Tokushima University, Tokushima, Japan.
Ajay GoelDepartment of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute of City of Hope, Biomedical Research Center, Monrovia, California, USA. ajgoel@coh.org.

Funding

Noncoding RNA Biomarkers for Noninvasive and Early Detection of Pancreatic CancerU01CA214254 · NCI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI Ajay Goel, DANIEL D VON HOFF · 2017 to 2026
$8.9M
Exosomal biomarkers for the early detection of hepatocellular carcinomaR01CA271443 · NCI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI Ajay Goel · 2023 to 2026
$2.9M
Aspirin and Cancer Prevention in Lynch Syndrome: From Cell to Population DataU01CA187956 · NCI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI GOEL, AJAY, WODARZ, DOMINIK F · 2014 to 2018
$2.7M
Development of microRNA Biomarkers For Noninvasive Detection of Colorectal CancerR01CA184792 · NCI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI GOEL, AJAY · 2015 to 2019
$1.8M
METHYLATION BIOMARKER DEVELOPMENT FOR NONINVASIVE DETECTION OF COLORECTAL CANCERR01CA181572 · NCI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI GOEL, AJAY · 2014 to 2018
$1.6M
5mC and 5hmC DNA alterations as sensitive and specific biomarkers for the non-invasive early detection of pancreatic ductal adenocarcinomaU01CA296639 · NCI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI Ajay Goel · 2025 to 2026
$1.4M
NCI NIH HHS R01 CA181572NCI NIH HHS R01 CA184792NCI NIH HHS R01 CA271443NCI NIH HHS U01 CA187956NCI NIH HHS U01 CA214254NCI NIH HHS U01 CA296639NIH HHS CA181572, CA184792, CA187956, CA214254, CA271443, and CA296639.
6 · The paper itself

Abstract

Glucagon-like peptide-1 receptor agonists (GLP-1RAs), widely used for diabetes and obesity, have recently attracted attention for potential anti-tumor effects, although their mechanisms remain unclear. Given their role in metabolic regulation, we hypothesized that GLP-1RAs may target cancer-specific metabolic vulnerabilities. Hepatocellular carcinoma (HCC) is characterized by metabolic reprogramming and enhanced glycolysis, which contribute to therapeutic resistance. Here, we investigated the anti-tumor effects of a GLP-1RA in HCC, focusing on its ability to modulate glycolytic pathways and enhance sensitivity to Lenvatinib. Lenvatinib-resistant HCC cells exhibited suppressed AMPKα1 and increased HIF-1α and PFKFB3 expression, promoting glycolytic adaptation. GLP-1RA treatment restored AMPKα1 activity while suppressing HIF-1α/PFKFB3 signaling, thereby reducing glycolytic activity and enhancing apoptosis. Combination treatment with GLP-1RA and Lenvatinib significantly inhibited tumor cell growth in resistant models. These findings suggest that the AMPKα1/HIF-1α/PFKFB3 axis represents a metabolic vulnerability in Lenvatinib-resistant HCC and support GLP-1RA-based combination strategies.

Identifiers

PMID42373728
PMCPMC13680616

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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.