Evidence map›Paper›PMID 27129180›Full record

ArticleOncotarget2016

Sorafenib-resistant hepatocellular carcinoma stratified by phosphorylated ERK activates PD-1 immune checkpoint.

Jiang Chen, Tong Ji, Jie Zhao, Gaofeng Li, Jian Zhang, Renan Jin, Jinghua Liu, Xiaolong Liu, Xiao Liang, Diyu Huang and 4 more

Registry-linked trialOpen access · diamondAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06584435 (A Single-arm Study of Toripalimab in Adjuvant Therapy After Resection of High-risk Renal Cancer), which is not on this map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
4.4field-weighted citation impact, top 5% of its field
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.

NCT06584435 phase2active not recruitingnot on this mapstarted 2022, after this paper: background citation

A Single-arm Study of Toripalimab in Adjuvant Therapy After Resection of High-risk Renal Cancer

TypeinterventionalSponsorTianjin Medical University Second HospitalRan2022 to 2027Enrolled100ConditionsHigh-risk Renal Cell CarcinomaArmsToripalimab
3 · Its place in the literature

Who cites it

28 citing papers in PubMed, 44 citations in OpenAlex.

  1. Trial
  2. Review
  3. Review
  4. Article
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  8. Review
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  10. Article
  11. Tumor-infiltrating CD8Drug discovery today · 2021
    Review
  12. Review
  13. Review
  14. Liver Fibrosis and Inflammation under the Control of ERK2.International journal of molecular sciences · 2020
    Article
  15. Article
  16. Review
  17. Article
  18. NTranslational cancer research · 2020
    Article
  19. Article
  20. 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

14 authors at 2 institutions in 1 country.

Jiang ChenDepartment of General Surgery, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310058, China.
Tong JiLife Sciences Institute and Innovation Center for Cell Signalling Network, Zhejiang University, Hangzhou, Zhejiang, 310029, China.
Jie ZhaoDepartment of General Surgery, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310058, China.
Gaofeng LiLife Sciences Institute and Innovation Center for Cell Signalling Network, Zhejiang University, Hangzhou, Zhejiang, 310029, China.
Jian ZhangDepartment of General Surgery, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310058, China.
Renan JinDepartment of General Surgery, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310058, China.
Jinghua LiuDepartment of General Surgery, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310058, China.
Xiaolong LiuDepartment of General Surgery, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310058, China.
Xiao LiangDepartment of General Surgery, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310058, China.
Diyu HuangDepartment of General Surgery, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310058, China.
Anyong XieDepartment of General Surgery, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310058, China.
Hui LinDepartment of General Surgery, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310058, China.
Yong CangLife Sciences Institute and Innovation Center for Cell Signalling Network, Zhejiang University, Hangzhou, Zhejiang, 310029, China.
Xiujun CaiDepartment of General Surgery, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310058, China.
Zhejiang University · CNSir Run Run Shaw Hospital · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Sorafenib is a multikinase inhibitor approved as the first line treatment for late stage hepatocellular carcinoma (HCC). Due to its significant variation in clinical benefits among patients, defining prognostic biomarkers for sorafenib sensitivity in HCC would allow targeted treatment. Phosphorylated extracellular signaling-regulated kinase (pERK) was proposed to predict the response to sorafenib in HCC, but clinical supports are mixed or even contradictory. Here we found that pERK expression levels are variable in different nodules from individual patient liver. Xenografts derived from resected tumors are resistant to sorafenib inhibition when expressing low levels of pERK. This correlation of low pERK levels and sorafenib resistance is corroborated by histological characterization of chemical-induced and genetic mouse models for pERK-positive and pERK-negative HCC respectively, as well as computed tomography (CT) imaging of patient tumors with validated pERK expression. Mouse and human HCC samples expressing low pERK show strong inflammatory infiltrating cells and significant enrichment of intratumoral CD8+ cytotoxic T lymphocytes that express programmed death receptor-1 (PD-1). These pERK-PD-1+ patients have poorer overall and disease-free survival than pERK+PD-1- patients. In conclusion, our data suggest that anti-PD-1 immunotherapy might complement sorafenib in treating HCC patients by targeting sorafenib-resistant cancer cells, and the dual pERK and PD-1 biomarkers would help HCC patient selection to achieve optimal clinical benefits.

Indexed as

Drug Resistance, NeoplasmAnimalsCarcinoma, HepatocellularCell Cycle CheckpointsCell Line, TumorExtracellular Signal-Regulated MAP KinasesFemaleHep G2 CellsHumansK562 CellsLiver NeoplasmsMiceMice, NudeMice, TransgenicNiacinamidePhenylurea CompoundsExtracellular Signal-Regulated MAP KinasesNiacinamidePDCD1 protein, humanPhenylurea CompoundsProgrammed Cell Death 1 ReceptorSorafenibhepatocellular carcinoma(HCC)phosphorylated extracellular signaling-regulated kinase(pERK)programmed death receptor-1 (PD-1)sorafenib

Identifiers

PMID27129180
PMCPMC5173058
OpenAlexW2344413712

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

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.