Evidence map›Paper›PMID 36831438›Full record

ArticleCancers2023

Association between Plasminogen Activator Inhibitor-1 and Osimertinib Tolerance in EGFR-Mutated Lung Cancer via Epithelial-Mesenchymal Transition.

Kentaro Tokumo, Takeshi Masuda, Taku Nakashima, Masashi Namba, Kakuhiro Yamaguchi, Shinjiro Sakamoto, Yasushi Horimasu, Shintaro Miyamoto, Hiroshi Iwamoto, Kazunori Fujitaka and 4 more

Open access · goldAbstract read
In one paragraph

Article in Cancers, 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
2.1field-weighted citation impact, top 13% 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, 8 citations in OpenAlex.

  1. Article
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  5. Review
  6. 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

14 authors at 2 institutions in 1 country.

Kentaro TokumoDepartment of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.ORCID 0000-0002-6062-876X
Takeshi MasudaDepartment of Respiratory Medicine, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.ORCID 0000-0003-3557-0049
Taku NakashimaDepartment of Respiratory Medicine, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.
Masashi NambaDepartment of Clinical Oncology, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.ORCID 0000-0002-8019-9800
Kakuhiro YamaguchiDepartment of Respiratory Medicine, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.ORCID 0000-0002-9117-1934
Shinjiro SakamotoDepartment of Respiratory Medicine, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.
Yasushi HorimasuDepartment of Respiratory Medicine, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.ORCID 0000-0002-3390-8491
Shintaro MiyamotoDepartment of Respiratory Medicine, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.
Hiroshi IwamotoDepartment of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.ORCID 0000-0003-4922-5334
Kazunori FujitakaDepartment of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.
Yoshihiro MiyataDepartment of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima 734-8551, Japan.
Morihito OkadaDepartment of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima 734-8551, Japan.
Hironobu HamadaDepartment of Physical Analysis and Therapeutic Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.ORCID 0000-0002-7979-0708
Noboru HattoriDepartment of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.
Hiroshima University · JPHiroshima University Hospital · JP

Funding

grants-in-aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan no. 18K15952
6 · The paper itself

Abstract

Most epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC) cells are killed within a few days after osimertinib treatment; however, surviving cells remain detectable and are called drug-tolerant cells. Plasminogen activator inhibitor-1 (PAI-1) was reported to be involved in chemotherapeutic or radiotherapeutic resistance. The purpose of the present study was to investigate whether PAI-1 is involved in osimertinib tolerance and whether it could be a therapeutic target for overcoming this tolerance. We showed that the PAI-1 mRNA expression levels and mesenchymal gene expression levels were significantly higher in drug-tolerant EGFR-mutated NSCLC cells than in control cells after 7 days of in vitro osimertinib treatment. Additionally, an RNA microarray analysis revealed upregulation of the integrin-induced EMT pathway in osimertinib-tolerant cells. Furthermore, we observed that PAI-1 inhibitors suppressed proliferation and the degree of epithelial-mesenchymal transition (EMT) in tolerant cells. Finally, in a subcutaneous tumor model, we showed that combining osimertinib with a PAI-1 inhibitor prevented the regrowth of tumors comprising EGFR-mutated cancer cells. The present study is the first to show PAI-1 to be involved in tolerance to osimertinib via EMT.

Indexed as

drug-tolerant cellsepidermal growth factor receptorepithelial–mesenchymal transitionnon-small-cell lung cancerplasminogen activator inhibitor-1

Identifiers

PMID36831438
PMCPMC9954529
OpenAlexW4319759458

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.