Evidence map›Paper›PMID 36416133›Full record

ArticleCancer medicine2023

MET kinase inhibitor reverses resistance to entrectinib induced by hepatocyte growth factor in tumors with NTRK1 or ROS1 rearrangements.

Yohei Takumi, Sachiko Arai, Chiaki Suzuki, Koji Fukuda, Akihiro Nishiyama, Shinji Takeuchi, Hiroki Sato, Kunio Matsumoto, Kenji Sugio, Seiji Yano

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

Article in Cancer medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.9field-weighted citation impact, top 24% 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

6 citing papers in PubMed, 6 citations in OpenAlex.

  1. Article
  2. Therapeutic advances of targeting receptor tyrosine kinases in cancer.Signal transduction and targeted therapy · 2024
    Review
  3. Article
  4. Article
  5. Review
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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 2 institutions in 1 country.

Yohei TakumiDivision of Medical Oncology, Cancer Research Institute, Kanazawa University, Kanazawa, Japan.ORCID 0000-0002-1171-9243
Sachiko AraiDivision of Medical Oncology, Cancer Research Institute, Kanazawa University, Kanazawa, Japan.
Chiaki SuzukiDivision of Medical Oncology, Cancer Research Institute, Kanazawa University, Kanazawa, Japan.
Koji FukudaDivision of Medical Oncology, Cancer Research Institute, Kanazawa University, Kanazawa, Japan.
Akihiro NishiyamaDivision of Medical Oncology, Cancer Research Institute, Kanazawa University, Kanazawa, Japan.
Shinji TakeuchiDivision of Medical Oncology, Cancer Research Institute, Kanazawa University, Kanazawa, Japan.
Hiroki SatoDivision of Tumor Dynamics and Regulation, Cancer Research Institute, Kanazawa University, Kanazawa, Japan.
Kunio MatsumotoDivision of Tumor Dynamics and Regulation, Cancer Research Institute, Kanazawa University, Kanazawa, Japan.
Kenji SugioDepartment of Thoracic and Breast Surgery, Faculty of Medicine, Oita University, Yufu, Japan.
Seiji YanoDivision of Medical Oncology, Cancer Research Institute, Kanazawa University, Kanazawa, Japan.
Kanazawa University · JPOita University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundEntrectinib is an effective drug for treating solid tumors with NTRK gene rearrangement and non-small cell lung cancer (NSCLC) with ROS1 gene rearrangement. However, its efficacy is limited by tolerance and acquired resistance, the mechanisms of which are not fully understood. The growth factors produced by the tumor microenvironment, including hepatocyte growth factor (HGF) produced by tumor-associated fibroblasts, critically affect the sensitivity to targeted drugs.

methodsWe investigated whether growth factors that can be produced by the microenvironment affect sensitivity of NTRK1-rearranged colon cancer KM12SM cells and ROS1-rearranged NSCLC HCC78 cells to entrectinib both in vitro and in vivo.

resultsAmong the growth factors assessed, HGF most potently induced entrectinib resistance in KM12SM and HCC78 cells by activating its receptor MET. HGF-induced entrectinib resistance was reversed by the active-HGF-specific macrocyclic peptide HiP-8 and the MET kinase inhibitor capmatinib in vitro. In addition, HGF-producing fibroblasts promoted entrectinib resistance in vitro (culture model) and in vivo (subcutaneous tumor model). The use of capmatinib circumvented entrectinib resistance in a subcutaneous tumor model inoculated with KM12SM and HGF-producing fibroblasts.

conclusionOur findings suggest that growth factors in the tumor microenvironment, such as HGF, may induce resistance to entrectinib in tumors with NTRK1 or ROS1 rearrangements. Our results further suggest that optimally co-administering inhibitors of resistance-inducing growth factors may maximize the therapeutic efficacy of entrectinib.

Indexed as

Antineoplastic AgentsCarcinoma, Non-Small-Cell LungLung NeoplasmsBenzamidesHepatocyte Growth FactorHumansImidazolesIndazolesProtein Kinase InhibitorsProtein-Tyrosine KinasesProto-Oncogene ProteinsReceptor Protein-Tyrosine KinasesReceptor, trkATriazinesTumor MicroenvironmentAntineoplastic AgentsBenzamidescapmatinibentrectinibHepatocyte Growth FactorHGF protein, humanImidazolesIndazolesNTRK1 protein, humanProtein Kinase InhibitorsProtein-Tyrosine KinasesProto-Oncogene ProteinsReceptor Protein-Tyrosine KinasesReceptor, trkAROS1 protein, humanTriazinesentrectinibHGFMETNTRKROS1

Identifiers

PMID36416133
PMCPMC10028024
OpenAlexW4309746947

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LicenceCC BY
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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.