Functional dissection of the KRAS G12C mutation by comparison among multiple oncogenic driver mutations in a lung cancer cell line model

Keigo Kobayashi; Hideki Terai; Hiroyuki Yasuda; Junko Hamamoto; Yuichiro Hayashi; Osamu Takeuchi; Yoichiro Mitsuishi; Keita Masuzawa; Tadashi Manabe; Shinnosuke Ikemura; Ichiro Kawada; Yukio Suzuki; Kenzo Soejima; Koichi Fukunaga

doi:10.1016/j.bbrc.2020.11.110

Functional dissection of the KRAS G12C mutation by comparison among multiple oncogenic driver mutations in a lung cancer cell line model

Keigo Kobayashi, Hideki Terai, Hiroyuki Yasuda, Junko Hamamoto, Yuichiro Hayashi, Osamu Takeuchi, Yoichiro Mitsuishi, Keita Masuzawa, Tadashi Manabe, Shinnosuke Ikemura, Ichiro Kawada, Yukio Suzuki, Kenzo Soejima, Koichi Fukunaga

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

Abstract

The development of molecular targeted therapy has improved clinical outcomes in patients with life-threatening advanced lung cancers with driver oncogenes. However, selective treatment for KRAS-mutant lung cancer remains underdeveloped. We have successfully characterised specific molecular and pathological features of KRAS-mutant lung cancer utilising newly developed cell line models that can elucidate the differences in driver oncogenes among tissues with identical genetic backgrounds. Among these KRAS-mutation-associated specific features, we focused on the IGF2-IGF1R pathway, which has been implicated in the drug resistance mechanisms to AMG 510, a recently developed selective inhibitor of KRAS G12C lung cancer. Experimental data derived from our cell line model can be used as a tool for clinical treatment strategy development through understanding of the biology of lung cancer. The model developed in this paper may help understand the mechanism of anticancer drug resistance in KRAS-mutated lung cancer and help develop new targeted therapies to treat patients with this disease.

Original language	English
Pages (from-to)	1-7
Number of pages	7
Journal	Biochemical and Biophysical Research Communications
Volume	534
DOIs	https://doi.org/10.1016/j.bbrc.2020.11.110
Publication status	Published - 2021 Jan 1
Externally published	Yes

Keywords

AMG510
IGF1R
KRAS G12C
Lung cancer

ASJC Scopus subject areas

Biophysics
Biochemistry
Molecular Biology
Cell Biology

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Kobayashi, K., Terai, H., Yasuda, H., Hamamoto, J., Hayashi, Y., Takeuchi, O., Mitsuishi, Y., Masuzawa, K., Manabe, T., Ikemura, S., Kawada, I., Suzuki, Y., Soejima, K., & Fukunaga, K. (2021). Functional dissection of the KRAS G12C mutation by comparison among multiple oncogenic driver mutations in a lung cancer cell line model. Biochemical and Biophysical Research Communications, 534, 1-7. https://doi.org/10.1016/j.bbrc.2020.11.110

Functional dissection of the KRAS G12C mutation by comparison among multiple oncogenic driver mutations in a lung cancer cell line model. / Kobayashi, Keigo; Terai, Hideki; Yasuda, Hiroyuki; Hamamoto, Junko; Hayashi, Yuichiro; Takeuchi, Osamu; Mitsuishi, Yoichiro; Masuzawa, Keita; Manabe, Tadashi; Ikemura, Shinnosuke ; Kawada, Ichiro; Suzuki, Yukio; Soejima, Kenzo ; Fukunaga, Koichi.

In: Biochemical and Biophysical Research Communications, Vol. 534, 01.01.2021, p. 1-7.

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

Kobayashi, K, Terai, H, Yasuda, H, Hamamoto, J, Hayashi, Y, Takeuchi, O, Mitsuishi, Y, Masuzawa, K, Manabe, T, Ikemura, S , Kawada, I, Suzuki, Y, Soejima, K & Fukunaga, K 2021, 'Functional dissection of the KRAS G12C mutation by comparison among multiple oncogenic driver mutations in a lung cancer cell line model', Biochemical and Biophysical Research Communications, vol. 534, pp. 1-7. https://doi.org/10.1016/j.bbrc.2020.11.110

Kobayashi, Keigo ; Terai, Hideki ; Yasuda, Hiroyuki ; Hamamoto, Junko ; Hayashi, Yuichiro ; Takeuchi, Osamu ; Mitsuishi, Yoichiro ; Masuzawa, Keita ; Manabe, Tadashi ; Ikemura, Shinnosuke ; Kawada, Ichiro ; Suzuki, Yukio ; Soejima, Kenzo ; Fukunaga, Koichi. / Functional dissection of the KRAS G12C mutation by comparison among multiple oncogenic driver mutations in a lung cancer cell line model. In: Biochemical and Biophysical Research Communications. 2021 ; Vol. 534. pp. 1-7.

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title = "Functional dissection of the KRAS G12C mutation by comparison among multiple oncogenic driver mutations in a lung cancer cell line model",

abstract = "The development of molecular targeted therapy has improved clinical outcomes in patients with life-threatening advanced lung cancers with driver oncogenes. However, selective treatment for KRAS-mutant lung cancer remains underdeveloped. We have successfully characterised specific molecular and pathological features of KRAS-mutant lung cancer utilising newly developed cell line models that can elucidate the differences in driver oncogenes among tissues with identical genetic backgrounds. Among these KRAS-mutation-associated specific features, we focused on the IGF2-IGF1R pathway, which has been implicated in the drug resistance mechanisms to AMG 510, a recently developed selective inhibitor of KRAS G12C lung cancer. Experimental data derived from our cell line model can be used as a tool for clinical treatment strategy development through understanding of the biology of lung cancer. The model developed in this paper may help understand the mechanism of anticancer drug resistance in KRAS-mutated lung cancer and help develop new targeted therapies to treat patients with this disease.",

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author = "Keigo Kobayashi and Hideki Terai and Hiroyuki Yasuda and Junko Hamamoto and Yuichiro Hayashi and Osamu Takeuchi and Yoichiro Mitsuishi and Keita Masuzawa and Tadashi Manabe and Shinnosuke Ikemura and Ichiro Kawada and Yukio Suzuki and Kenzo Soejima and Koichi Fukunaga",

note = "Funding Information: This work was supported in part by the Japan Society for the Promotion of Science to K. Soejima ( 19H03671 ), H. Yasuda ( 17K09667 ), and H. Terai ( 18K08184 ). This work was also supported in part by the grant provided by the Takeda Science Foundation to H. Yasuda and H. Terai, and by a grant provided by the Ichiro Kanehara Foundation to H. Terai. Publisher Copyright: {\textcopyright} 2020 The Authors",

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AU - Kobayashi, Keigo

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AU - Hayashi, Yuichiro

AU - Takeuchi, Osamu

AU - Mitsuishi, Yoichiro

AU - Masuzawa, Keita

AU - Manabe, Tadashi

AU - Ikemura, Shinnosuke

AU - Kawada, Ichiro

AU - Suzuki, Yukio

AU - Soejima, Kenzo

AU - Fukunaga, Koichi

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N2 - The development of molecular targeted therapy has improved clinical outcomes in patients with life-threatening advanced lung cancers with driver oncogenes. However, selective treatment for KRAS-mutant lung cancer remains underdeveloped. We have successfully characterised specific molecular and pathological features of KRAS-mutant lung cancer utilising newly developed cell line models that can elucidate the differences in driver oncogenes among tissues with identical genetic backgrounds. Among these KRAS-mutation-associated specific features, we focused on the IGF2-IGF1R pathway, which has been implicated in the drug resistance mechanisms to AMG 510, a recently developed selective inhibitor of KRAS G12C lung cancer. Experimental data derived from our cell line model can be used as a tool for clinical treatment strategy development through understanding of the biology of lung cancer. The model developed in this paper may help understand the mechanism of anticancer drug resistance in KRAS-mutated lung cancer and help develop new targeted therapies to treat patients with this disease.

AB - The development of molecular targeted therapy has improved clinical outcomes in patients with life-threatening advanced lung cancers with driver oncogenes. However, selective treatment for KRAS-mutant lung cancer remains underdeveloped. We have successfully characterised specific molecular and pathological features of KRAS-mutant lung cancer utilising newly developed cell line models that can elucidate the differences in driver oncogenes among tissues with identical genetic backgrounds. Among these KRAS-mutation-associated specific features, we focused on the IGF2-IGF1R pathway, which has been implicated in the drug resistance mechanisms to AMG 510, a recently developed selective inhibitor of KRAS G12C lung cancer. Experimental data derived from our cell line model can be used as a tool for clinical treatment strategy development through understanding of the biology of lung cancer. The model developed in this paper may help understand the mechanism of anticancer drug resistance in KRAS-mutated lung cancer and help develop new targeted therapies to treat patients with this disease.

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Functional dissection of the KRAS G12C mutation by comparison among multiple oncogenic driver mutations in a lung cancer cell line model

Abstract

Keywords

ASJC Scopus subject areas

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