Evidence map›Paper›PMID 40044981›Full record

ArticleBritish journal of cancer2025

EphB4-ephrin-B2 are targets in castration resistant prostate cancer.

Grace Xiuqing Li, Binyun Ma, Shaobing Zhang, Ren Liu, Imran N Siddiqi, Akash Sali, Anthony El-Khoueiry, Mitchell Gross, Bodour Salhia, Sarmad Sadeghi and 1 more

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Article in British journal of cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

11 authors.

Grace Xiuqing LiDepartment of Medicine, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Binyun MaDepartment of Medicine, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Shaobing ZhangDepartment of Medicine, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Ren LiuMerck Pharmaceutical Inc. Previous: Department of Medicine, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Imran N SiddiqiDepartment of Pathology, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Akash SaliCatherine & Joseph Aresty Department of Urology, USC Institute of Urology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Anthony El-KhoueiryDepartment of Medicine, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Mitchell GrossDepartment of Medicine, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Bodour SalhiaDepartment of Translational Genomics, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Sarmad SadeghiDepartment of Medicine, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Parkash S GillDepartment of Medicine, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. parkashg@med.usc.edu.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundPI3K pathway activation is a common and early event in prostate cancer, from loss of function mutations in PTEN, or activating mutations in PIK3Ca or AKT leading to constitutive activation, induction of growth factor-receptors kinase EphB4 and its ligand ephrin-B2. We hypothesized that induction of EphB4 is an early event required for tumor initiation. Secondly, we hypothesized that EphB4 remains relevant when prostate cancer becomes androgen independent.

methodsGenetic mouse model of conditional PTEN deletion in prostate epithelium induces tumor in all mice. We tested this model against EPHB4 wild type and deleted in prostate epithelium. This allowed us to test its role in tumor initiation. We also tested an orthogonal approach by using decoy soluble EphB4 to block bidirectional signaling resulting from EphB4-ephrin-B2 interaction. Role of EphB4-ephrin-B2 in androgen deprived mice was tested for role in refractory cancer model.

resultsPTEN deletion induces EphB4 and ephrin-B2 in prostate cancer which was substantially reduced when EPHB4 is deleted in the same prostate epithelial cells. sEphB4-alb fusion protein with improved pharmacokinetics similarly inhibited tumor formation, thus establishing the role in tumor initiation. sEphB4-alb retained the efficacy in castration resistant androgen independent prostate cancer. We have thus observed that induction of EphB4 is required for the initiation of prostate cancer in PTEN null mouse and that signaling downstream from EphB4 is required in androgen deprivation and thus castration resistant prostate cancer. Pharmacological inhibition of EphB4 pathway reproduced the results. Targeting EphB4 should be tested in prostate cancer especially those resistant to androgen deprivation therapy.

conclusionsEphB4 and ephrin-B2 receptor ligand pair is induced in PTEN null prostate cancer, which significantly contributes to the tumor initiation. Secondly, EphB4-ephrin-B2 pathway continue to promote tumor progression even in androgen deprivation and thus hormone refractory tumor. EphB4-ephrin-B2 may be candidates for precision medicine with biomarker-based patient selection with and without concurrent standard of care.

Indexed as

Ephrin-B2Prostatic Neoplasms, Castration-ResistantReceptor, EphB4AnimalsHumansMaleMicePTEN PhosphohydrolaseSignal TransductionEphb4 protein, mouseEphrin-B2PTEN PhosphohydrolasePten protein, mouseReceptor, EphB4

Identifiers

PMID40044981
PMCPMC11997055

What Socratic holds

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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 Socratic graph.