Evidence map›Paper›PMID 41927886›Full record

ArticleNPJ precision oncology2026

AXL-SHC1 signaling axis mediates adaptive resistance to HER2-targeted tyrosine kinase inhibitors in HER2-aberrant lung and gastric cancers.

Masaki Ishida, Tadaaki Yamada, Yuki Katayama, Hayato Kawachi, Ryo Sawada, Ryota Nakamura, Soichi Hirai, Yohei Matsui, Kenji Morimoto, Keisuke Onoi and 18 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in NPJ precision oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. 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

28 authors.

Masaki IshidaDepartment of Pulmonary Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465, Kajii-cho, Kamigyo-ku, Kyoto, Japan.
Tadaaki YamadaDepartment of Pulmonary Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465, Kajii-cho, Kamigyo-ku, Kyoto, Japan. tayamada@koto.kpu-m.ac.jp.
Yuki KatayamaDepartment of Pulmonary Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465, Kajii-cho, Kamigyo-ku, Kyoto, Japan.
Hayato KawachiDepartment of Pulmonary Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465, Kajii-cho, Kamigyo-ku, Kyoto, Japan.
Ryo SawadaDepartment of Pulmonary Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465, Kajii-cho, Kamigyo-ku, Kyoto, Japan.
Ryota NakamuraDepartment of Pulmonary Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465, Kajii-cho, Kamigyo-ku, Kyoto, Japan.
Soichi HiraiDepartment of Pulmonary Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465, Kajii-cho, Kamigyo-ku, Kyoto, Japan.
Yohei MatsuiDepartment of Pulmonary Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465, Kajii-cho, Kamigyo-ku, Kyoto, Japan.
Kenji MorimotoDepartment of Pulmonary Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465, Kajii-cho, Kamigyo-ku, Kyoto, Japan.
Keisuke OnoiDepartment of Pulmonary Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465, Kajii-cho, Kamigyo-ku, Kyoto, Japan.
Aosa Nakamura-SasadaDepartment of Pulmonary Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465, Kajii-cho, Kamigyo-ku, Kyoto, Japan.
Mano HorinakaDepartment of Drug Discovery Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465, Kajii-cho, Kamigyo-ku, Kyoto, Japan.
Toshiyuki SakaiDepartment of Drug Discovery Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465, Kajii-cho, Kamigyo-ku, Kyoto, Japan.
Tomoki SakakidaDepartment of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Toshifumi DoiDepartment of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Kazuo YasumotoDepartment of Medical Oncology, Kanazawa Medical University, Uchinada, Ishikawa, Japan.
Yasuhiro GotoDepartment of Respiratory Medicine, Fujita Health University School of Medicine, Toyoake, Aichi, Japan.
Naoki FuruyaDepartment of Respiratory Medicine, St. Marianna University School of Medicine, Kawasaki, Japan.
Hirokazu TaniguchiDepartment of Respiratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Hirokazu OginoDepartment of Respiratory Medicine and Rheumatology, Graduate School of Biomedical Sciences, Tokushima University, Tokushima, Japan.
Nakano TakayukiDepartment of Respiratory Medicine, Fukuchiyama City Hospital, Kyoto, Japan.
Yusuke ChiharaDepartment of Respiratory Medicine, Uji Tokushukai Medical Center, Uji, Kyoto, Japan.
Koji FukudaDivision of Innovative Cancer Control Research, Cancer Research Institute, Kanazawa University, Kanazawa, Japan.
Hiroaki TaniguchiDivision of Innovative Cancer Control Research, Cancer Research Institute, Kanazawa University, Kanazawa, Japan.
Hisanori UeharaDepartment of Diagnostic Pathology, Tokushima University Hospital, Tokushima, Japan.
Seiji YanoDivision of Innovative Cancer Control Research, Cancer Research Institute, Kanazawa University, Kanazawa, Japan.
Shinsaku TokudaDepartment of Pulmonary Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465, Kajii-cho, Kamigyo-ku, Kyoto, Japan.
Koichi TakayamaDepartment of Pulmonary Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465, Kajii-cho, Kamigyo-ku, Kyoto, Japan.

Funding

JSPS KAKENHI 23K07607
6 · The paper itself

Abstract

Human epidermal growth factor receptor 2 (HER2)-tyrosine kinase inhibitors (TKIs) are being developed for the treatment of patients with HER2-aberrant lung and gastric cancers. However, achieving complete tumor remission remains challenging. Here, we investigated the molecular mechanisms underlying adaptive resistance to HER2-TKIs in HER2-aberrant tumor cells in order to devise strategies to prevent the emergence of drug-tolerant cells. Our findings showed that the AXL receptor was activated by HER2-TKIs and maintained cell survival by interacting with epidermal growth factor receptor, HER2, and HER3. This process, mediated by the SHC1BP-SHC1 axis, contributed to adaptive resistance to HER2-TKIs in a subset of HER2-aberrant lung and gastric cancers. AXL inhibition significantly delayed tumor regrowth of AXL-overexpressing cells by enhancing HER2-TKI-induced apoptosis in xenograft models. These results suggest that patients with HER2-aberrant lung and gastric cancers exhibiting high AXL expression may benefit from an initial combination therapy with an AXL inhibitor.

Identifiers

PMID41927886
PMCPMC13046926

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