Evidence map›Paper›PMID 40934856›Full record

ReviewThe Journal of pharmacology and experimental therapeutics2025

PHLDA2 in cancer: From molecular mechanisms to therapeutic opportunities.

Qingqing Wan, Mi Zhang, Wantao Chen, Xu Wang

Abstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in The Journal of pharmacology and experimental therapeutics, 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

4 authors.

Qingqing WanDepartment of Oral and Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology; Shanghai Research Institute of Stomatology, Shanghai, China.
Mi ZhangDepartment of Oral and Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology; Shanghai Research Institute of Stomatology, Shanghai, China.
Wantao ChenDepartment of Oral and Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology; Shanghai Research Institute of Stomatology, Shanghai, China. Electronic address: chenwantao196323@sjtu.edu.cn.
Xu WangDepartment of Oral and Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology; Shanghai Research Institute of Stomatology, Shanghai, China. Electronic address: wangx312016@sh9hospital.org.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Pleckstrin homology-like domain, family A, member 2 (PHLDA2), an imprinted gene located on human chromosome 11p15.5, has emerged as a critical player in cancer biology with complex dual roles as both tumor suppressor and oncogene. This review synthesizes recent advances in understanding the mechanistic contributions of PHLDA2 to tumorigenesis, highlighting novel insights into its regulation of cellular processes, including apoptosis, autophagy, and ferroptosis, across diverse cancer types. We provide the first comprehensive comparative analysis of the context-dependent functions of PHLDA2, revealing how tumor microenvironment and cancer type determine its oncogenic versus tumor-suppressive roles. Key innovations addressed include the discovery of the role of PHLDA2 in ferroptosis through its interaction with ALOX12, its regulation of the PI3K/protein kinase B (AKT) pathway via competitive membrane binding, and its emerging potential as both a diagnostic biomarker and therapeutic target. The review critically examines current challenges in translating PHLDA2 research into clinical applications and identifies priority research directions for exploiting this protein's therapeutic potential in precision cancer medicine. SIGNIFICANCE STATEMENT: Pleckstrin homology-like domain, family A, member 2 functions as both oncogene and tumor suppressor across cancer types, regulating apoptosis, autophagy, and ferroptosis. Its dual roles and posttranslational modifications present novel opportunities for precision cancer diagnosis, prognosis, and targeted therapy development.

Indexed as

NeoplasmsNuclear ProteinsAnimalsApoptosisAutophagyFerroptosisHumansNuclear ProteinsTSSC3 proteinCancerFerroptosisImprinted genePHLDA2Pleckstrin homology domains

Identifiers

PMID40934856
PMCPMC12597642

What OpenQuestion 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 OpenQuestion graph.