Evidence map›Paper›PMID 32166604›Full record

ArticleMedical oncology (Northwood, London, England)2020

Activation of the HGF/c-MET axis promotes lenvatinib resistance in hepatocellular carcinoma cells with high c-MET expression.

Rongdang Fu, Shaotao Jiang, Jieyuan Li, Huanwei Chen, Xiaohong Zhang

Abstract read
PubMed Publisher
In one paragraph

Article in Medical oncology (Northwood, London, England), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
59citing papers in PubMed, 1 pooled it
9.8field-weighted citation impact, top 1% 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.

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

59 citing papers in PubMed, 1 synthesis or guideline pooled it, 110 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Hepatocellular carcinoma: signaling pathways and therapeutic advances.Signal transduction and targeted therapy · 2025
    Review
  11. Review
  12. Article
  13. Review
  14. Review
  15. Article
  16. Article
  17. Article
  18. Small-molecule-based targeted therapy in liver cancer.Molecular therapy : the journal of the American Society of Gene Therapy · 2024
    Review
  19. Review
  20. Review
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

5 authors at 3 institutions in 1 country.

Rongdang FuDepartment of Infectious Disease, The Third Affiliated Hospital of Sun Yat-Sen University, No.600 Tianhe Road, Tianhe District, Guangzhou, 510630, China.
Shaotao JiangDepartment of HBP Surgery II, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, China.
Jieyuan LiDepartment of Hepatic Surgery, The Affiliated Foshan Hospital of Sun Yat-Sen University, Foshan, 528000, China.
Huanwei ChenDepartment of Hepatic Surgery, The Affiliated Foshan Hospital of Sun Yat-Sen University, Foshan, 528000, China. chwei@fsyyy.com.
Xiaohong ZhangDepartment of Infectious Disease, The Third Affiliated Hospital of Sun Yat-Sen University, No.600 Tianhe Road, Tianhe District, Guangzhou, 510630, China. zhangxh58@outlook.com.
Foshan Hospital of TCM · CNGuangzhou First People's Hospital · CNSun Yat-sen University · CN

Funding

Medical Science and Technology Research Fund of Guangdong Province A2017387
6 · The paper itself

Abstract

Lenvatinib is a long-awaited alternative to sorafenib for the first-line targeted therapy of patients with advanced hepatocellular carcinoma (HCC). However, resistance to lenvatinib has also become a major obstacle to improving the prognosis of HCC patients. The underlying molecular mechanisms contributing to lenvatinib resistance in HCC are largely unknown. HGF/c-MET axis activation is related to tumor progression and several hallmarks of cancer and is considered as the key contributor to drug resistance. In the present study, we focused on the role of the HGF/c-MET axis in mediating lenvatinib resistance in HCC cells. We showed that HGF reduced the antiproliferative, proapoptotic, and anti-invasive effects of lenvatinib on HCC cells with high c-MET expression but did not significantly affect HCC cells with low c-MET expression. The c-MET inhibitor PHA-665752 rescued HCC cells from HGF-induced lenvatinib resistance. Furthermore, HGF/c-MET activated the downstream PI3K/AKT and MAPK/ERK pathways and promoted epithelial-mesenchymal transition (EMT) in HCC cells. Collectively, our results suggested that combining lenvatinib treatment with a c-MET inhibitor may improve its systemic therapeutic efficacy in HCC patients with high c-MET expression.

Indexed as

Drug Resistance, NeoplasmAntineoplastic AgentsApoptosisCarcinoma, HepatocellularCell Line, TumorCell ProliferationEpithelial-Mesenchymal TransitionHepatocyte Growth FactorHumansIndolesLiver NeoplasmsPhenylurea CompoundsProtein Kinase InhibitorsProto-Oncogene Proteins c-metQuinolinesSignal Transduction5-((2,6-dichlorobenzyl)sulfonyl)-3-((3,5-dimethyl-4-((2-(pyrrolidin-1-ylmethyl)pyrrolidin-1-yl)carbonyl)-1H-pyrrol-2-yl)methylene)-1,3-dihydro-2H-indol-2-oneAntineoplastic AgentsHepatocyte Growth FactorHGF protein, humanIndoleslenvatinibMET protein, humanPhenylurea CompoundsProtein Kinase InhibitorsProto-Oncogene Proteins c-metQuinolinesSulfonesc-METHepatocellular carcinomaHGFLenvatinibResistance

Identifiers

PMID32166604
OpenAlexW3011857315

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.