Evidence map›Paper›PMID 41459907›Full record

ArticleOncotarget2025

Nerofe+ldDox releases c-Jun from nuclear ST2 to reprogram the immune microenvironment in mtKRAS tumors.

Joel Ohana, Uziel Sandler, Benjamin A Weinberg, Stephen Liu, Yoram Devary

Erratum issuedAbstract readClinical Trial, Phase I
In one paragraph

Article in Oncotarget, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

5 authors.

Joel Ohana
Uziel Sandler
Benjamin A Weinberg
Stephen Liu
Yoram Devary

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND/

objectivesMutant KRAS (mtKRAS) tumors are highly immunosuppressive, largely through secretion of IL-10 and TGF-β2, which prevent immune cell infiltration. Nerofe (dTCApFs), a peptide derivative of Tumor Cell Apoptosis Factor, induces endoplasmic reticulum stress and modulates immune signaling through the T1/ST2 receptor, which is overexpressed in mtKRAS tumors. We evaluated whether combining Nerofe with low-dose doxorubicin (ldDox) could remodel the immune microenvironment and overcome tumor immunosuppression.

methods

resultsNerofe+ldDox treatment increased IL-2 and suppressed IL-10 in PANC-1 cells, reversing the immunosuppressive cytokine profile. Patient biopsies confirmed these effects, showing higher IL-2, lower IL-10, and increased infiltration of NK cells, CD8

conclusionsNerofe+ldDox reprograms the immune microenvironment of mtKRAS tumors by releasing c-Jun from inhibitory nuclear ST2, enabling expression of IL-2 and miR-217. This "nuclear immunomodulation" promotes immune cell infiltration and downregulates KRAS expression, highlighting Nerofe+ldDox as a promising therapeutic approach for mtKRAS-driven cancers.

Indexed as

Antineoplastic Combined Chemotherapy ProtocolsDoxorubicinPancreatic NeoplasmsProto-Oncogene Proteins c-junProto-Oncogene Proteins p21(ras)Tumor MicroenvironmentCell Line, TumorFemaleHumansMaleMiddle AgedMutationDoxorubicinKRAS protein, humanProto-Oncogene Proteins c-junProto-Oncogene Proteins p21(ras)mutant KRASNerofenuclear immunomodulationST2 Receptortumor immune microenvironment

Identifiers

PMID41459907
PMCPMC12750723

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Registered trials

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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.