GSK3 inhibition circumvents and overcomes acquired lorlatinib resistance in ALK-rearranged non-small-cell lung cancer

Abstract Anaplastic lymphoma kinase (ALK) fusion is found in ~3%–5% of patients with non-small-cell lung cancers (NSCLCs). Although the third-generation ALK tyrosine kinase inhibitor (TKI) lorlatinib shows high clinical efficacy in ALK-positive NSCLC, most of the patients eventually relapse with acq...
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Autor*in:	Yuki Shimizu [verfasserIn] Koutaroh Okada [verfasserIn] Jun Adachi [verfasserIn] Yuichi Abe [verfasserIn] Ryohei Narumi [verfasserIn] Ken Uchibori [verfasserIn] Noriko Yanagitani [verfasserIn] Sumie Koike [verfasserIn] Satoshi Takagi [verfasserIn] Makoto Nishio [verfasserIn] Naoya Fujita [verfasserIn] Ryohei Katayama [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2022

Übergeordnetes Werk:	In: npj Precision Oncology - Nature Portfolio, 2017, 6(2022), 1, Seite 13
Übergeordnetes Werk:	volume:6 ; year:2022 ; number:1 ; pages:13

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1038/s41698-022-00260-0

Katalog-ID:	DOAJ046499032

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520			\|a Abstract Anaplastic lymphoma kinase (ALK) fusion is found in ~3%–5% of patients with non-small-cell lung cancers (NSCLCs). Although the third-generation ALK tyrosine kinase inhibitor (TKI) lorlatinib shows high clinical efficacy in ALK-positive NSCLC, most of the patients eventually relapse with acquired resistance. Recently, drug-tolerant persister (DTP) cells have been considered an important seed of acquired resistance cells. In this study, we established lorlatinib intermediate resistant cells from a patient-derived cell model. Glycogen synthase kinase 3 (GSK3) inhibitions significantly suppressed lorlatinib intermediate resistant cell growth. GSK3 inhibition also sensitized acquired resistance cells derived from alectinib-treated patients with or without secondary mutations to lorlatinib. Therefore, GSK3 plays a crucial role in developing acquired resistance against lorlatinib in ALK-positive NSCLC mediated by lorlatinib intermediate resistant cells and could be a potential molecular target to prevent acquired lorlatinib resistance and overcome ALK-TKI resistance.
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allfields	10.1038/s41698-022-00260-0 doi (DE-627)DOAJ046499032 (DE-599)DOAJc2a1926a23da4e888e277aae73418fe6 DE-627 ger DE-627 rakwb eng RC254-282 Yuki Shimizu verfasserin aut GSK3 inhibition circumvents and overcomes acquired lorlatinib resistance in ALK-rearranged non-small-cell lung cancer 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Anaplastic lymphoma kinase (ALK) fusion is found in ~3%–5% of patients with non-small-cell lung cancers (NSCLCs). Although the third-generation ALK tyrosine kinase inhibitor (TKI) lorlatinib shows high clinical efficacy in ALK-positive NSCLC, most of the patients eventually relapse with acquired resistance. Recently, drug-tolerant persister (DTP) cells have been considered an important seed of acquired resistance cells. In this study, we established lorlatinib intermediate resistant cells from a patient-derived cell model. Glycogen synthase kinase 3 (GSK3) inhibitions significantly suppressed lorlatinib intermediate resistant cell growth. GSK3 inhibition also sensitized acquired resistance cells derived from alectinib-treated patients with or without secondary mutations to lorlatinib. Therefore, GSK3 plays a crucial role in developing acquired resistance against lorlatinib in ALK-positive NSCLC mediated by lorlatinib intermediate resistant cells and could be a potential molecular target to prevent acquired lorlatinib resistance and overcome ALK-TKI resistance. Neoplasms. Tumors. Oncology. Including cancer and carcinogens Koutaroh Okada verfasserin aut Jun Adachi verfasserin aut Yuichi Abe verfasserin aut Ryohei Narumi verfasserin aut Ken Uchibori verfasserin aut Noriko Yanagitani verfasserin aut Sumie Koike verfasserin aut Satoshi Takagi verfasserin aut Makoto Nishio verfasserin aut Naoya Fujita verfasserin aut Ryohei Katayama verfasserin aut In npj Precision Oncology Nature Portfolio, 2017 6(2022), 1, Seite 13 (DE-627)884384454 (DE-600)2891458-2 2397768X nnns volume:6 year:2022 number:1 pages:13 https://doi.org/10.1038/s41698-022-00260-0 kostenfrei https://doaj.org/article/c2a1926a23da4e888e277aae73418fe6 kostenfrei https://doi.org/10.1038/s41698-022-00260-0 kostenfrei https://doaj.org/toc/2397-768X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 6 2022 1 13
spelling	10.1038/s41698-022-00260-0 doi (DE-627)DOAJ046499032 (DE-599)DOAJc2a1926a23da4e888e277aae73418fe6 DE-627 ger DE-627 rakwb eng RC254-282 Yuki Shimizu verfasserin aut GSK3 inhibition circumvents and overcomes acquired lorlatinib resistance in ALK-rearranged non-small-cell lung cancer 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Anaplastic lymphoma kinase (ALK) fusion is found in ~3%–5% of patients with non-small-cell lung cancers (NSCLCs). Although the third-generation ALK tyrosine kinase inhibitor (TKI) lorlatinib shows high clinical efficacy in ALK-positive NSCLC, most of the patients eventually relapse with acquired resistance. Recently, drug-tolerant persister (DTP) cells have been considered an important seed of acquired resistance cells. In this study, we established lorlatinib intermediate resistant cells from a patient-derived cell model. Glycogen synthase kinase 3 (GSK3) inhibitions significantly suppressed lorlatinib intermediate resistant cell growth. GSK3 inhibition also sensitized acquired resistance cells derived from alectinib-treated patients with or without secondary mutations to lorlatinib. Therefore, GSK3 plays a crucial role in developing acquired resistance against lorlatinib in ALK-positive NSCLC mediated by lorlatinib intermediate resistant cells and could be a potential molecular target to prevent acquired lorlatinib resistance and overcome ALK-TKI resistance. Neoplasms. Tumors. Oncology. Including cancer and carcinogens Koutaroh Okada verfasserin aut Jun Adachi verfasserin aut Yuichi Abe verfasserin aut Ryohei Narumi verfasserin aut Ken Uchibori verfasserin aut Noriko Yanagitani verfasserin aut Sumie Koike verfasserin aut Satoshi Takagi verfasserin aut Makoto Nishio verfasserin aut Naoya Fujita verfasserin aut Ryohei Katayama verfasserin aut In npj Precision Oncology Nature Portfolio, 2017 6(2022), 1, Seite 13 (DE-627)884384454 (DE-600)2891458-2 2397768X nnns volume:6 year:2022 number:1 pages:13 https://doi.org/10.1038/s41698-022-00260-0 kostenfrei https://doaj.org/article/c2a1926a23da4e888e277aae73418fe6 kostenfrei https://doi.org/10.1038/s41698-022-00260-0 kostenfrei https://doaj.org/toc/2397-768X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 6 2022 1 13
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authorswithroles_txt_mv	Yuki Shimizu @@aut@@ Koutaroh Okada @@aut@@ Jun Adachi @@aut@@ Yuichi Abe @@aut@@ Ryohei Narumi @@aut@@ Ken Uchibori @@aut@@ Noriko Yanagitani @@aut@@ Sumie Koike @@aut@@ Satoshi Takagi @@aut@@ Makoto Nishio @@aut@@ Naoya Fujita @@aut@@ Ryohei Katayama @@aut@@
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callnumber-first	R - Medicine
author	Yuki Shimizu
spellingShingle	Yuki Shimizu misc RC254-282 misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens GSK3 inhibition circumvents and overcomes acquired lorlatinib resistance in ALK-rearranged non-small-cell lung cancer
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topic_title	RC254-282 GSK3 inhibition circumvents and overcomes acquired lorlatinib resistance in ALK-rearranged non-small-cell lung cancer
topic	misc RC254-282 misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens
topic_unstemmed	misc RC254-282 misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens
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title	GSK3 inhibition circumvents and overcomes acquired lorlatinib resistance in ALK-rearranged non-small-cell lung cancer
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title_full	GSK3 inhibition circumvents and overcomes acquired lorlatinib resistance in ALK-rearranged non-small-cell lung cancer
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author_browse	Yuki Shimizu Koutaroh Okada Jun Adachi Yuichi Abe Ryohei Narumi Ken Uchibori Noriko Yanagitani Sumie Koike Satoshi Takagi Makoto Nishio Naoya Fujita Ryohei Katayama
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title_sort	gsk3 inhibition circumvents and overcomes acquired lorlatinib resistance in alk-rearranged non-small-cell lung cancer
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title_auth	GSK3 inhibition circumvents and overcomes acquired lorlatinib resistance in ALK-rearranged non-small-cell lung cancer
abstract	Abstract Anaplastic lymphoma kinase (ALK) fusion is found in ~3%–5% of patients with non-small-cell lung cancers (NSCLCs). Although the third-generation ALK tyrosine kinase inhibitor (TKI) lorlatinib shows high clinical efficacy in ALK-positive NSCLC, most of the patients eventually relapse with acquired resistance. Recently, drug-tolerant persister (DTP) cells have been considered an important seed of acquired resistance cells. In this study, we established lorlatinib intermediate resistant cells from a patient-derived cell model. Glycogen synthase kinase 3 (GSK3) inhibitions significantly suppressed lorlatinib intermediate resistant cell growth. GSK3 inhibition also sensitized acquired resistance cells derived from alectinib-treated patients with or without secondary mutations to lorlatinib. Therefore, GSK3 plays a crucial role in developing acquired resistance against lorlatinib in ALK-positive NSCLC mediated by lorlatinib intermediate resistant cells and could be a potential molecular target to prevent acquired lorlatinib resistance and overcome ALK-TKI resistance.
abstractGer	Abstract Anaplastic lymphoma kinase (ALK) fusion is found in ~3%–5% of patients with non-small-cell lung cancers (NSCLCs). Although the third-generation ALK tyrosine kinase inhibitor (TKI) lorlatinib shows high clinical efficacy in ALK-positive NSCLC, most of the patients eventually relapse with acquired resistance. Recently, drug-tolerant persister (DTP) cells have been considered an important seed of acquired resistance cells. In this study, we established lorlatinib intermediate resistant cells from a patient-derived cell model. Glycogen synthase kinase 3 (GSK3) inhibitions significantly suppressed lorlatinib intermediate resistant cell growth. GSK3 inhibition also sensitized acquired resistance cells derived from alectinib-treated patients with or without secondary mutations to lorlatinib. Therefore, GSK3 plays a crucial role in developing acquired resistance against lorlatinib in ALK-positive NSCLC mediated by lorlatinib intermediate resistant cells and could be a potential molecular target to prevent acquired lorlatinib resistance and overcome ALK-TKI resistance.
abstract_unstemmed	Abstract Anaplastic lymphoma kinase (ALK) fusion is found in ~3%–5% of patients with non-small-cell lung cancers (NSCLCs). Although the third-generation ALK tyrosine kinase inhibitor (TKI) lorlatinib shows high clinical efficacy in ALK-positive NSCLC, most of the patients eventually relapse with acquired resistance. Recently, drug-tolerant persister (DTP) cells have been considered an important seed of acquired resistance cells. In this study, we established lorlatinib intermediate resistant cells from a patient-derived cell model. Glycogen synthase kinase 3 (GSK3) inhibitions significantly suppressed lorlatinib intermediate resistant cell growth. GSK3 inhibition also sensitized acquired resistance cells derived from alectinib-treated patients with or without secondary mutations to lorlatinib. Therefore, GSK3 plays a crucial role in developing acquired resistance against lorlatinib in ALK-positive NSCLC mediated by lorlatinib intermediate resistant cells and could be a potential molecular target to prevent acquired lorlatinib resistance and overcome ALK-TKI resistance.
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title_short	GSK3 inhibition circumvents and overcomes acquired lorlatinib resistance in ALK-rearranged non-small-cell lung cancer
url	https://doi.org/10.1038/s41698-022-00260-0 https://doaj.org/article/c2a1926a23da4e888e277aae73418fe6 https://doaj.org/toc/2397-768X
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up_date	2024-07-03T20:59:51.122Z
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GSK3 inhibition circumvents and overcomes acquired lorlatinib resistance in ALK-rearranged non-small-cell lung cancer

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