Evidence map›Paper›PMID 28164434›Full record

ArticleMolecular oncology2017

Dual inhibition of Akt and c-Met as a second-line therapy following acquired resistance to sorafenib in hepatocellular carcinoma cells.

Peng Han, Hali Li, Xian Jiang, Bo Zhai, Gang Tan, Dali Zhao, Haiquan Qiao, Bing Liu, Hongchi Jiang, Xueying Sun

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular oncology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed, 1 pooled it
4.8field-weighted citation impact, top 4% 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

47 citing papers in PubMed, 1 synthesis or guideline pooled it, 70 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Review
  5. Article
  6. Review
  7. Review
  8. Review
  9. Article
  10. Review
  11. [The companion diagnostics of targeted therapy and immunotherapy for hepatocellular carcinoma].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2022
    Article
  12. Review
  13. Article
  14. c-Met up-regulates the expression of PD-L1 through MAPK/NF-κBp65 pathway.Journal of molecular medicine (Berlin, Germany) · 2022
    Article
  15. Review
  16. Review
  17. Article
  18. Article
  19. Review
  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

10 authors at 3 institutions in 1 country.

Peng HanThe Hepatosplenic Surgery Center, Department of General Surgery, the First Affiliated Hospital of Harbin Medical University, China.
Hali LiThe Hepatosplenic Surgery Center, Department of General Surgery, the First Affiliated Hospital of Harbin Medical University, China.
Xian JiangThe Hepatosplenic Surgery Center, Department of General Surgery, the First Affiliated Hospital of Harbin Medical University, China.
Bo ZhaiThe Hepatosplenic Surgery Center, Department of General Surgery, the First Affiliated Hospital of Harbin Medical University, China.
Gang TanDepartment of General Surgery, the Fourth Affiliated Hospital of Harbin Medical University, China.
Dali ZhaoThe Hepatosplenic Surgery Center, Department of General Surgery, the First Affiliated Hospital of Harbin Medical University, China.
Haiquan QiaoThe Hepatosplenic Surgery Center, Department of General Surgery, the First Affiliated Hospital of Harbin Medical University, China.
Bing LiuThe Hepatosplenic Surgery Center, Department of General Surgery, the First Affiliated Hospital of Harbin Medical University, China.
Hongchi JiangThe Hepatosplenic Surgery Center, Department of General Surgery, the First Affiliated Hospital of Harbin Medical University, China.
Xueying SunThe Hepatosplenic Surgery Center, Department of General Surgery, the First Affiliated Hospital of Harbin Medical University, China.
Harbin Medical University · CNFirst Affiliated Hospital of Harbin Medical University · CNFourth Affiliated Hospital of Harbin Medical University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Sorafenib displays a limited efficacy for advanced hepatocellular carcinoma (HCC). Some patients with HCC initially respond to sorafenib, but eventually succumb to the disease, indicating that the acquired resistance to sorafenib reduces its beneficial effects. No alternative drugs are available after the failure of sorafenib therapy. Therefore, investigation of the mechanisms underlying the acquired resistance and development of second-line treatments for sorafenib-resistant HCC are urgently required. In this study, sorafenib-resistant HCC cells generated from sorafenib-sensitive human HCC cells were shown to overproduce hepatocyte growth factor (HGF) and overexpress c-Met kinase and its phosphorylated form, leading to the activation of Akt and ERK (extracellular signaling-regulated kinase) pathways. Use of specific c-Met inhibitors enhanced the effects of sorafenib by inhibiting the growth of sorafenib-resistant HCC cells. Akt inhibitors, a class of second-line therapeutic drugs under investigation for treating HCC in clinical trials, enhanced the effects of sorafenib, but also activated the c-Met pathway in sorafenib-resistant cells. Dual inhibition of Akt and c-Met by their respective inhibitors, MK2206 and capmatinib, additively or synergistically suppressed sorafenib-resistant HCC cells in vitro and sorafenib-resistant HCC xenografts in mice. The anticancer activities of MK2206 mainly rely on its ability to induce cell apoptosis and autophagic death, while capmatinib treatment leads to cell cycle arrest at phase G1. These results provide strong evidence for further investigation on the clinical utility of dual inhibition of Akt and c-Met, particularly MK2206 and capmatinib, as a second-line therapy for advanced HCC that has acquired resistance to sorafenib.

Indexed as

AnimalsAntineoplastic AgentsCarcinoma, HepatocellularCell Line, TumorDrug Resistance, NeoplasmHep G2 CellsHumansLiverLiver NeoplasmsMaleMice, Inbred BALB CNiacinamidePhenylurea CompoundsProtein Kinase InhibitorsProto-Oncogene Proteins c-aktProto-Oncogene Proteins c-metAntineoplastic AgentsMET protein, humanNiacinamidePhenylurea CompoundsProtein Kinase InhibitorsProto-Oncogene Proteins c-aktProto-Oncogene Proteins c-metPTEN PhosphohydrolaseSorafenibacquired resistanceAktcellular signaling pathwayc-Methepatocellular carcinomasorafenib

Identifiers

PMID28164434
PMCPMC5527443
OpenAlexW2587486788

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.