Evidence map›Paper›PMID 42583674›Full record

ArticleLivers2026

Decoding the Complexity of Hepatocellular Carcinoma: Clinical Challenges and Targeting HuR as a Novel Therapeutic Strategy.

Elizabeth Jones, Natalie Eppler, Forkan Ahamed, Yuxia Zhang

Abstract read
In one paragraph

Article in Livers, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. 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

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.

Elizabeth JonesDepartment of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, MS 1018, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA.ORCID 0000-0002-8938-7277
Natalie EpplerDepartment of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, MS 1018, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA.
Forkan AhamedDepartment of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, MS 1018, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA.
Yuxia ZhangDepartment of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, MS 1018, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA.ORCID 0000-0001-9951-3583

Funding

RNA-binding protein HuR in liver pathophysiology and carcinogenesisR01DK119131 · NIDDK · UNIVERSITY OF KANSAS MEDICAL CENTER · PI ZHANG, YUXIA · 2019 to 2023
$1.8M
NIDDK NIH HHS R01 DK119131
6 · The paper itself

Abstract

Background: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide and remains a major therapeutic challenge due to its marked inter- and intratumoral heterogeneity, diverse etiologies, and high propensity for therapeutic resistance. This review summarizes the biological complexity of HCC and current therapeutic challenges, with a particular focus on the RNA-binding protein human antigen R (HuR) as an emerging therapeutic target. Methods: A comprehensive narrative review of peer-reviewed literature was conducted, focusing on HCC pathogenesis, molecular heterogeneity, tumor microenvironment, mechanisms of therapeutic resistance, and recent advances in treatment. Emphasis was placed on studies investigating the biological functions of HuR and its therapeutic potential in HCC. Results: HCC progression is driven by complex interactions among genetic, epigenetic, metabolic, and environmental factors, resulting in substantial tumor heterogeneity and variable therapeutic responses. Dysregulated oncogenic signaling and immunosuppressive tumor microenvironment collectively contribute to resistance against current therapies, including multikinase inhibitors and immune checkpoint inhibitors. Although emerging strategies, such as combination immunotherapy, metabolic targeting, epigenetic modulation, and precision medicine, have shown encouraging preclinical and clinical results, their efficacy remains limited by tumor complexity and adaptive resistance. HuR functions as a master post-transcriptional regulator that stabilizes and promotes the translation of numerous mRNAs encoding oncogenic, inflammatory, and pro-survival factors. Accumulating preclinical evidence demonstrates that pharmacological inhibition of HuR suppresses multiple tumor-promoting pathways and enhances therapeutic sensitivity, supporting its potential as a novel therapeutic strategy for HCC. Conclusions: The biological complexity of HCC necessitates multifaceted, precision-based therapeutic approaches. Although additional HCC-specific mechanistic and translational studies are needed, targeting HuR represents a promising strategy to overcome tumor heterogeneity, therapeutic resistance, and disease progression. Continued integration of molecular profiling, advanced omics technologies, and rational combination therapies will be essential for translating these advances into improved clinical outcomes for patients with HCC.

Indexed as

clinical challengecomplexityhepatocellular carcinomahuman antigen R (HuR)novel therapeutic strategypost-transcriptional regulation

Identifiers

PMID42583674
PMCPMC13461241

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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.