Evidence mapPaperPMID 41570933Full record

ReviewCancer letters2026

Midkine (MDK) as a central regulator of the tumor microenvironment: From developmental cytokine to therapeutic target.

Hareesh B Nair, Ajay Nair, Ya-Guang Liu, Dileep K Vijayan, Ramadevi Subramani, Rajkumar Lakshmanaswamy, Suryavathi Viswanadhapalli, Gangadhara R Sareddy, Surinder K Batra, Ratna K Vadlamudi

Abstract readReview
In one paragraph

Review in Cancer letters, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing 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

8 citing papers in PubMed.

  1. Article
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  8. Article
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

10 authors.

Hareesh B NairDepartment of Molecular and Translational Medicine, Texas Tech University Health Science Center, El Paso, TX, 79905, USA. Electronic address: hbhaskar@ttuhsc.edu.
Ajay NairSchool of Medicine, Amrita Vishwa Vidyapeetham, Kochi, Kerala, 682041, India.
Ya-Guang LiuDepartment of Pathology and Laboratory Medicine, University of Texas Health San Antonio, San Antonio, TX, USA.
Dileep K VijayanLaboratory for Computational and Structural Biology, Jubilee Centre for Medical Research, Thrissur, India.
Ramadevi SubramaniDepartment of Molecular and Translational Medicine, Texas Tech University Health Science Center, El Paso, TX, 79905, USA.
Rajkumar LakshmanaswamyDepartment of Molecular and Translational Medicine, Texas Tech University Health Science Center, El Paso, TX, 79905, USA.
Suryavathi ViswanadhapalliDepartment of Obstetrics and Gynecology, University of Texas Health San Antonio, San Antonio, TX, USA.
Gangadhara R SareddyDepartment of Obstetrics and Gynecology, University of Texas Health San Antonio, San Antonio, TX, USA.
Surinder K BatraDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.
Ratna K VadlamudiDepartment of Obstetrics and Gynecology, University of Texas Health San Antonio, San Antonio, TX, USA; Audie L. Murphy South Texas Veterans Health Care System, San Antonio, TX, USA.

Funding

Development of new therapeutic approaches for endometrial cancerR01CA267893 · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · 2025 to 2025
$709k
Novel targeted therapy for treating Ovarian CancerR01CA266970 · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · 2025 to 2025
$659k
BLRD VA I01 BX006280NCI NIH HHS R01 CA266970NCI NIH HHS R01 CA267893NCI NIH HHS R44 CA235991
6 · The paper itself

Abstract

Midkine (MDK) is an oncofetal, heparin-binding cytokine that is re-expressed across diverse cancers and correlates with aggressive disease and treatment resistance. This review synthesizes current evidence on MDK as a coordinator of tumor-intrinsic signaling and microenvironmental remodeling. We summarize MDK structural features, extracellular matrix interactions, and receptor systems that mediate MDK signaling, highlighting LRP1 and PTPRZ1 with context-dependent participation of ALK, nucleolin and integrins. Downstream, MDK engages MAPK, PI3K-AKT, STAT3 and NF-κB pathways to promote tumor cell survival, epithelial-mesenchymal plasticity, and therapeutic stress tolerance. We then focus on tumor microenvironment (TME) programs shaped by MDK, including angiogenesis, fibroblast activation and extracellular matrix remodeling, and the establishment of immunosuppressive niches. Across tumor types, MDK is linked to impaired dendritic-cell function, polarization of tumor-associated macrophages, accrual of myeloid-derived suppressor cells and reduced CD8

Indexed as

MidkineNeoplasmsTumor MicroenvironmentAnimalsHumansSignal TransductionMDK protein, humanMidkineAngiogenesisBiomarkersCancer-associated fibroblastsHematologic malignanciesImmune evasionImmunotherapyLigand-receptor interactionsMDKSingle cell transcriptomicsSolid tumorsTMETumor immune suppression

Identifiers

PMID41570933
PMCPMC12860532

What Socratic holds

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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.