Evidence map›Paper›PMID 40917745›Full record

ReviewFrontiers in cell and developmental biology2025

Targeting Wnt-driven metabolic adaptations in cancer: integrating glycolysis, glutaminolysis, IDO1-mediated immune evasion, and therapeutic delivery strategies.

Eric Flores-Hernández, Grace Binder, Kuo-Ching Mei, Nydia Tejeda-Muñoz

Abstract readReview
In one paragraph

Review in Frontiers in cell and developmental biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
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

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.

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

6 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Review
  6. Review
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

4 authors.

Eric Flores-HernándezDepartamento de Biología Celular, Facultad de Ciencias, Universidad Nacional Autónoma de México (UNAM), Mexico City, Mexico.
Grace BinderDepartment of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, United States.
Kuo-Ching MeiDepartment of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, State University of New York at Binghamton, Binghamton, NY, United States.
Nydia Tejeda-MuñozDepartment of Oncology Science, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The Wnt pathway is an evolutionarily conserved signaling cascade that regulates a wide range of fundamental cellular processes, including proliferation, differentiation, polarity, migration, metabolism, and survival. Due to its central regulatory roles, Wnt signaling is critically involved in the pathophysiology of numerous human diseases. Aberrant activation or insufficient inhibition of this pathway has been causally linked to cancer, degenerative disorders, metabolic syndromes, and developmental abnormalities. Wnt signaling drives cancer progression by reprogramming metabolism and promoting immune evasion. Wnt-driven tumors exhibit enhanced aerobic glycolysis (the Warburg effect), glutaminolysis, and macropinocytosis, which support rapid proliferation and help maintain redox homeostasis under nutrient-limited or nutrient-deprived conditions. These metabolic adaptations sustain tumor survival and contribute to immune suppression, as seen in the Wnt5a-indoleamine 2,3-dioxygenase 1 (IDO1) axis, which fosters regulatory T-cell expansion and an immunosuppressive microenvironment. The interplay among glycolysis, glutamine metabolism, and immune escape renders Wnt-driven cancers highly adaptable and resistant to conventional therapies. Targeting metabolic enzymes, such as pyruvate dehydrogenase kinase 1 (PDK1), lactate dehydrogenase A (LDHA), glutaminase (GLS), and monocarboxylate transporters (MCT-1), alongside immune checkpoint inhibitors or IDO1 blockade, presents a promising strategy for overcoming metabolic plasticity and immune evasion in Wnt-driven malignancies, thereby enhancing therapeutic efficacy and improving patient survival in otherwise refractory tumor types. Combining glycolysis and glutaminolysis inhibitors with T-cell activating therapies may disrupt tumor metabolic plasticity and restore anti-tumor immunity. Additionally, advanced drug delivery systems, including lipid nanoparticles (LNPs), polymeric nanocarriers, and exosome-based platforms, enhance the targeted accumulation of metabolic inhibitors and immunomodulatory agents while minimizing systemic toxicity. This review examines the metabolic and immune adaptations of Wnt-driven cancers, with a focus on glycolysis, glutaminolysis, and macropinocytosis. We highlight emerging therapeutic targets and nanomedicine-based delivery strategies to counteract metabolic adaptation and immune suppression. By integrating metabolic and immune-targeting with precision nano-delivery platforms, future treatment paradigms may improve outcomes for aggressive and therapy-resistant Wnt-driven cancers.

Indexed as

colorectal cancermacropinocytosismembrane traffickingmetabolic reprogrammingtargeted cancer therapiesWnt signaling

Identifiers

PMID40917745
PMCPMC12411565

What Socratic holds

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LicenceCC BY
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Registered trials

None linked

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 Socratic graph.