Ganetespib in epidermal growth factor receptor-tyrosine kinase inhibitor-resistant non-small cell lung cancer

Eisuke Kurihara; Kazuhiko Shien; Hidejiro Torigoe; Tatsuaki Takeda; Yuta Takahashi; Yusuke Ogoshi; Takahiro Yoshioka; Kei Namba; Hiroki Sato; Ken Suzawa; Hiromasa Yamamoto; Junichi Sou; Mikio Okazaki; Tadahiko Shien; Shuta Tomida; Shinichi Toyooka

doi:10.21873/anticanres.13283

Ganetespib in epidermal growth factor receptor-tyrosine kinase inhibitor-resistant non-small cell lung cancer

Eisuke Kurihara, Kazuhiko Shien, Hidejiro Torigoe, Tatsuaki Takeda, Yuta Takahashi, Yusuke Ogoshi, Takahiro Yoshioka, Kei Namba, Hiroki Sato, Ken Suzawa, Hiromasa Yamamoto, Junichi Sou, Mikio Okazaki, Tadahiko Shien, Shuta Tomida, Shinichi Toyooka

Research output: Contribution to journal › Article › peer-review

9 Citations (Scopus)

Abstract

Background: The 90-kDa heat-shock protein (HSP90) is a chaperone protein expressed at high levels in cancer cells and is involved in the folding or stabilization of several client proteins, including epidermal growth factor receptor (EGFR). Ganetespib is a second-generation HSP90 inhibitor with a potent antitumor effect against various cancer types. Materials and Methods: This study examined the antitumor effect of ganetespib in EGFR-mutant non-small cell lung cancer (NSCLC) cells and experimentally established EGFR-tyrosine kinase inhibitor (TKI)-resistant cells harboring various resistance mechanisms, including EGFR T790M mutation, met proto-oncogene amplification, and epithelial–mesenchymal transition. Results: Ganetespib showed a potent antitumor effect at low concentrations, suppressing EGFR-related downstream pathway molecules and inducing cleavage of poly ADP-ribose polymerase in all examined EGFR-TKI-resistant cell lines in vitro. Ganetespib also inhibited in vivo tumor growth in resistant cells harboring EGFR T790M. Conclusion: Ganetespib might be a promising

Original language	English
Pages (from-to)	1767-1775
Number of pages	9
Journal	Anticancer research
Volume	39
Issue number	4
DOIs	https://doi.org/10.21873/anticanres.13283
Publication status	Published - Apr 2019

Keywords

Acquired drug resistance
EGFR-TKI
Ganetespib
HSP90 inhibitor
Non-small cell lung cancer

ASJC Scopus subject areas

Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.21873/anticanres.13283

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Kurihara, E., Shien, K., Torigoe, H., Takeda, T., Takahashi, Y., Ogoshi, Y., Yoshioka, T., Namba, K., Sato, H., Suzawa, K., Yamamoto, H., Sou, J., Okazaki, M., Shien, T., Tomida, S., & Toyooka, S. (2019). Ganetespib in epidermal growth factor receptor-tyrosine kinase inhibitor-resistant non-small cell lung cancer. Anticancer research, 39(4), 1767-1775. https://doi.org/10.21873/anticanres.13283

Kurihara, E, Shien, K, Torigoe, H, Takeda, T, Takahashi, Y, Ogoshi, Y, Yoshioka, T, Namba, K, Sato, H, Suzawa, K , Yamamoto, H, Sou, J, Okazaki, M , Shien, T , Tomida, S & Toyooka, S 2019, 'Ganetespib in epidermal growth factor receptor-tyrosine kinase inhibitor-resistant non-small cell lung cancer', Anticancer research, vol. 39, no. 4, pp. 1767-1775. https://doi.org/10.21873/anticanres.13283

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title = "Ganetespib in epidermal growth factor receptor-tyrosine kinase inhibitor-resistant non-small cell lung cancer",

abstract = "Background: The 90-kDa heat-shock protein (HSP90) is a chaperone protein expressed at high levels in cancer cells and is involved in the folding or stabilization of several client proteins, including epidermal growth factor receptor (EGFR). Ganetespib is a second-generation HSP90 inhibitor with a potent antitumor effect against various cancer types. Materials and Methods: This study examined the antitumor effect of ganetespib in EGFR-mutant non-small cell lung cancer (NSCLC) cells and experimentally established EGFR-tyrosine kinase inhibitor (TKI)-resistant cells harboring various resistance mechanisms, including EGFR T790M mutation, met proto-oncogene amplification, and epithelial–mesenchymal transition. Results: Ganetespib showed a potent antitumor effect at low concentrations, suppressing EGFR-related downstream pathway molecules and inducing cleavage of poly ADP-ribose polymerase in all examined EGFR-TKI-resistant cell lines in vitro. Ganetespib also inhibited in vivo tumor growth in resistant cells harboring EGFR T790M. Conclusion: Ganetespib might be a promising",

keywords = "Acquired drug resistance, EGFR-TKI, Ganetespib, HSP90 inhibitor, Non-small cell lung cancer",

author = "Eisuke Kurihara and Kazuhiko Shien and Hidejiro Torigoe and Tatsuaki Takeda and Yuta Takahashi and Yusuke Ogoshi and Takahiro Yoshioka and Kei Namba and Hiroki Sato and Ken Suzawa and Hiromasa Yamamoto and Junichi Sou and Mikio Okazaki and Tadahiko Shien and Shuta Tomida and Shinichi Toyooka",

note = "Funding Information: The Authors thank Ms. Fumiko Isobe (Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan) for her technical support. This work was supported by a Management Expenses Grant and a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (JSPS KAKENHI grant numbers 17K16608 to K. Shien; 16H05431 to S. Toyooka). Publisher Copyright: {\textcopyright} 2019 International Institute of Anticancer Research. All rights reserved.",

year = "2019",

month = apr,

doi = "10.21873/anticanres.13283",

language = "English",

volume = "39",

pages = "1767--1775",

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T1 - Ganetespib in epidermal growth factor receptor-tyrosine kinase inhibitor-resistant non-small cell lung cancer

AU - Kurihara, Eisuke

AU - Shien, Kazuhiko

AU - Torigoe, Hidejiro

AU - Takeda, Tatsuaki

AU - Takahashi, Yuta

AU - Ogoshi, Yusuke

AU - Yoshioka, Takahiro

AU - Namba, Kei

AU - Sato, Hiroki

AU - Suzawa, Ken

AU - Yamamoto, Hiromasa

AU - Sou, Junichi

AU - Okazaki, Mikio

AU - Shien, Tadahiko

AU - Tomida, Shuta

AU - Toyooka, Shinichi

N1 - Funding Information: The Authors thank Ms. Fumiko Isobe (Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan) for her technical support. This work was supported by a Management Expenses Grant and a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (JSPS KAKENHI grant numbers 17K16608 to K. Shien; 16H05431 to S. Toyooka). Publisher Copyright: © 2019 International Institute of Anticancer Research. All rights reserved.

PY - 2019/4

Y1 - 2019/4

N2 - Background: The 90-kDa heat-shock protein (HSP90) is a chaperone protein expressed at high levels in cancer cells and is involved in the folding or stabilization of several client proteins, including epidermal growth factor receptor (EGFR). Ganetespib is a second-generation HSP90 inhibitor with a potent antitumor effect against various cancer types. Materials and Methods: This study examined the antitumor effect of ganetespib in EGFR-mutant non-small cell lung cancer (NSCLC) cells and experimentally established EGFR-tyrosine kinase inhibitor (TKI)-resistant cells harboring various resistance mechanisms, including EGFR T790M mutation, met proto-oncogene amplification, and epithelial–mesenchymal transition. Results: Ganetespib showed a potent antitumor effect at low concentrations, suppressing EGFR-related downstream pathway molecules and inducing cleavage of poly ADP-ribose polymerase in all examined EGFR-TKI-resistant cell lines in vitro. Ganetespib also inhibited in vivo tumor growth in resistant cells harboring EGFR T790M. Conclusion: Ganetespib might be a promising

AB - Background: The 90-kDa heat-shock protein (HSP90) is a chaperone protein expressed at high levels in cancer cells and is involved in the folding or stabilization of several client proteins, including epidermal growth factor receptor (EGFR). Ganetespib is a second-generation HSP90 inhibitor with a potent antitumor effect against various cancer types. Materials and Methods: This study examined the antitumor effect of ganetespib in EGFR-mutant non-small cell lung cancer (NSCLC) cells and experimentally established EGFR-tyrosine kinase inhibitor (TKI)-resistant cells harboring various resistance mechanisms, including EGFR T790M mutation, met proto-oncogene amplification, and epithelial–mesenchymal transition. Results: Ganetespib showed a potent antitumor effect at low concentrations, suppressing EGFR-related downstream pathway molecules and inducing cleavage of poly ADP-ribose polymerase in all examined EGFR-TKI-resistant cell lines in vitro. Ganetespib also inhibited in vivo tumor growth in resistant cells harboring EGFR T790M. Conclusion: Ganetespib might be a promising

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ER -

Ganetespib in epidermal growth factor receptor-tyrosine kinase inhibitor-resistant non-small cell lung cancer

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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