Evidence map›Paper›PMID 30651547›Full record

ArticleNature communications2019

AXL confers intrinsic resistance to osimertinib and advances the emergence of tolerant cells.

Hirokazu Taniguchi, Tadaaki Yamada, Rong Wang, Keiko Tanimura, Yuta Adachi, Akihiro Nishiyama, Azusa Tanimoto, Shinji Takeuchi, Luiz H Araujo, Mariana Boroni and 14 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 250 papers.

0numbers the graph read from it
0cells of the map it votes in
250citing papers in PubMed
17.2field-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

250 citing papers in PubMed, 354 citations in OpenAlex.

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190 more citing papers are in PubMed but not listed here.

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

24 authors at 10 institutions in 3 countries.

Hirokazu TaniguchiDivision of Medical Oncology, Cancer Research Institute, Kanazawa University, 13-1, Takara-machi, Kanazawa, 920-0934, Japan.ORCID http://orcid.org/0000-0003-2414-8344
Tadaaki YamadaDivision of Medical Oncology, Cancer Research Institute, Kanazawa University, 13-1, Takara-machi, Kanazawa, 920-0934, Japan. tayamada@koto.kpu-m.ac.jp.ORCID http://orcid.org/0000-0002-6945-281X
Rong WangDivision of Medical Oncology, Cancer Research Institute, Kanazawa University, 13-1, Takara-machi, Kanazawa, 920-0934, Japan.
Keiko TanimuraDepartment of Pulmonary Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465, Kajii-cho, Kamigyo-ku, Kyoto, 602-8566, Japan.
Yuta AdachiDivision of Medical Oncology, Cancer Research Institute, Kanazawa University, 13-1, Takara-machi, Kanazawa, 920-0934, Japan.
Akihiro NishiyamaDivision of Medical Oncology, Cancer Research Institute, Kanazawa University, 13-1, Takara-machi, Kanazawa, 920-0934, Japan.
Azusa TanimotoDivision of Medical Oncology, Cancer Research Institute, Kanazawa University, 13-1, Takara-machi, Kanazawa, 920-0934, Japan.
Shinji TakeuchiDivision of Medical Oncology, Cancer Research Institute, Kanazawa University, 13-1, Takara-machi, Kanazawa, 920-0934, Japan.
Luiz H AraujoDivision of Clinical Research, Brazilian National Cancer Institute, Rua André Cavalcanti 37, Rio de Janeiro - RJ, 20231-050, Brazil.
Mariana BoroniDivision of Experimental and Translational Research, Bioinformatics and Computational Biology Lab, Brazilian National Cancer Institute, Rua André Cavalcanti 37, Rio de Janeiro - RJ, 20231-050, Brazil.
Akihiro YoshimuraDepartment of Pulmonary Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465, Kajii-cho, Kamigyo-ku, Kyoto, 602-8566, Japan.
Shinsuke ShiotsuDepartment of Respiratory Medicine, Japanese Red Cross Kyoto Daiichi Hospital, 15-749 Hon-machi, Higashiyama-ku, Kyoto, 605-0981, Japan.
Isao MatsumotoDepartment of Thoracic, Cardiovascular and General Surgery, Kanazawa University, 13-1, Takara-machi, Kanazawa, 920-0934, Japan.
Satoshi WatanabeDepartment of Respiratory Medicine and Infectious Diseases, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata, 951-8510, Japan.
Toshiaki KikuchiDepartment of Respiratory Medicine and Infectious Diseases, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata, 951-8510, Japan.
Satoru MiuraDepartment of Internal Medicine, Niigata Cancer Center Hospital, 2-15-3 Kawagishi-cho, Niigata, 961-8566, Japan.
Hiroshi TanakaDepartment of Internal Medicine, Niigata Cancer Center Hospital, 2-15-3 Kawagishi-cho, Niigata, 961-8566, Japan.
Takeshi KitazakiDepartment of Respiratory Medicine, Japanese Red Cross Nagasaki Genbaku Hospital, 3-15 Mori-machi, Nagasaki, 852-8511, Japan.
Hiroyuki YamaguchiDepartment of Respiratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan.
Hiroshi MukaeDepartment of Respiratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan.
Junji UchinoDepartment of Pulmonary Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465, Kajii-cho, Kamigyo-ku, Kyoto, 602-8566, Japan.
Hisanori UeharaDepartment of Pathology and Laboratory Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15, Kuramoto-cho, Tokushima, 770-8503, Japan.
Koichi TakayamaDepartment of Pulmonary Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465, Kajii-cho, Kamigyo-ku, Kyoto, 602-8566, Japan.
Seiji YanoDivision of Medical Oncology, Cancer Research Institute, Kanazawa University, 13-1, Takara-machi, Kanazawa, 920-0934, Japan. syano@staff.kanazawa-u.ac.jp.ORCID http://orcid.org/0000-0002-6151-2988
Kanazawa University · JPKyoto Prefectural University of Medicine · JPNagasaki University · JPNiigata Cancer Center Hospital · JPNiigata University Medical and Dental Hospital · JPInstituto Nacional de Câncer - INCA · BRJapanese Red Cross Society, Japan · JPKyoto first Red Cross hospital · JPTokushima University · JPTranslational Research in Oncology · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

A novel EGFR-tyrosine kinase inhibitor (TKI), osimertinib, has marked efficacy in patients with EGFR-mutated lung cancer. However, some patients show intrinsic resistance and an insufficient response to osimertinib. This study showed that osimertinib stimulated AXL by inhibiting a negative feedback loop. Activated AXL was associated with EGFR and HER3 in maintaining cell survival and inducing the emergence of cells tolerant to osimertinib. AXL inhibition reduced the viability of EGFR-mutated lung cancer cells overexpressing AXL that were exposed to osimertinib. The addition of an AXL inhibitor during either the initial or tolerant phases reduced tumor size and delayed tumor re-growth compared to osimertinib alone. AXL was highly expressed in clinical specimens of EGFR-mutated lung cancers and its high expression was associated with a low response rate to EGFR-TKI. These results indicated pivotal roles for AXL and its inhibition in the intrinsic resistance to osimertinib and the emergence of osimertinib-tolerant cells.

Indexed as

AcrylamidesAdenocarcinoma of LungAdultAniline CompoundsAnimalsAntineoplastic Combined Chemotherapy ProtocolsAxl Receptor Tyrosine KinaseCarcinoma, Non-Small-Cell LungCell Line, TumorCell SurvivalDisease-Free SurvivalDrug Resistance, NeoplasmErbB ReceptorsFemaleGene Knockdown TechniquesHeterocyclic Compounds, 2-RingAcrylamidesAniline CompoundsAxl Receptor Tyrosine KinaseEGFR protein, humanERBB3 protein, humanErbB ReceptorsHeterocyclic Compounds, 2-RingIndolesNPS-1034osimertinibPiperazinesProtein Kinase InhibitorsProto-Oncogene ProteinsPyrazolesPyrimidinesReceptor, ErbB-3Receptor Protein-Tyrosine KinasesRNA, Small Interfering

Identifiers

PMID30651547
PMCPMC6335418
OpenAlexW2910264472

What OpenQuestion holds

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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.