Taxane-Platin-Resistant Lung Cancers Co-develop Hypersensitivity to JumonjiC Demethylase Inhibitors

Autores: Dalvi, Maithili P.; Wang, Lei; Zhong, Rui; Kollipara, Rahul K.; Park, Hyunsil; Bayo Fina, Juan Miguel; Yenerall, Paul; Zhou, Yunyun; Timmons, Brenda C.; Rodriguez Canales, Jaime; Behrens, Carmen; Mino, Barbara; Villalobos, Pamela; Parra, Edwin R.; Suraokar, Milind; Pataer, Apar; Swisher, Stephen G.; Kalhor, Neda; Bhanu, Natarajan V.; Garcia, Benjamin A.; Heymach, John V.; Coombes, Kevin; Xie, Yang; Girard, Luc; Gazdar, Adi F.; Kittler, Ralf; Wistuba, Ignacio I.; Minna, John D.; Martinez, Elisabeth D.
Año de publicación: 2017
Idioma: inglés
Tipo de recurso: artículo
Estado: versión publicada
Descripción: Although non-small cell lung cancer (NSCLC) patients benefit from standard taxane-platin chemotherapy, many relapse, developing drug resistance. We established preclinical taxane-platin-chemoresistance models and identified a 35-gene resistance signature, which was associated with poor recurrence-free survival in neoadjuvant-treated NSCLC patients and included upregulation of the JumonjiC lysine demethylase KDM3B. In fact, multi-drug-resistant cells progressively increased the expression of many JumonjiC demethylases, had altered histone methylation, and, importantly, showed hypersensitivity to JumonjiC inhibitors in vitro and in vivo. Increasing taxane-platin resistance in progressive cell line series was accompanied by progressive sensitization to JIB-04 and GSK-J4. These JumonjiC inhibitors partly reversed deregulated transcriptional programs, prevented the emergence of drug-tolerant colonies from chemo-naive cells, and synergized with standard chemotherapy in vitro and in vivo. Our findings reveal JumonjiC inhibitors as promising therapies for targeting taxane-platin-chemoresistant NSCLCs.
Fil: Dalvi, Maithili P.. University of Texas. Southwestern Medical Center; Estados Unidos
Fil: Wang, Lei. University of Texas. Southwestern Medical Center; Estados Unidos
Fil: Zhong, Rui. University of Texas. Southwestern Medical Center; Estados Unidos
Fil: Kollipara, Rahul K.. University of Texas. Southwestern Medical Center; Estados Unidos
Fil: Park, Hyunsil. University of Texas. Southwestern Medical Center; Estados Unidos
Fil: Bayo Fina, Juan Miguel. University of Texas. Southwestern Medical Center; Estados Unidos. Universidad Austral. Facultad de Ciencias Biomédicas. Instituto de Investigaciones en Medicina Traslacional. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Medicina Traslacional; Argentina
Fil: Yenerall, Paul. University of Texas. Southwestern Medical Center; Estados Unidos
Fil: Zhou, Yunyun. University of Texas. Southwestern Medical Center; Estados Unidos
Fil: Timmons, Brenda C.. University of Texas. Southwestern Medical Center; Estados Unidos
Fil: Rodriguez Canales, Jaime. University of Texas; Estados Unidos
Fil: Behrens, Carmen. Md Anderson Cancer Center; Estados Unidos
Fil: Mino, Barbara. University of Texas; Estados Unidos
Fil: Villalobos, Pamela. University of Texas; Estados Unidos
Fil: Parra, Edwin R.. University of Texas; Estados Unidos
Fil: Suraokar, Milind. University of Texas; Estados Unidos
Fil: Pataer, Apar. University of Texas; Estados Unidos
Fil: Swisher, Stephen G.. University of Texas; Estados Unidos
Fil: Kalhor, Neda. University of Texas; Estados Unidos
Fil: Bhanu, Natarajan V.. University of Pennsylvania; Estados Unidos
Fil: Garcia, Benjamin A.. University of Pennsylvania; Estados Unidos
Fil: Heymach, John V.. University of Texas; Estados Unidos
Fil: Coombes, Kevin. University of Texas; Estados Unidos
Fil: Xie, Yang. University of Texas. Southwestern Medical Center; Estados Unidos
Fil: Girard, Luc. University of Texas. Southwestern Medical Center; Estados Unidos
Fil: Gazdar, Adi F.. University of Texas. Southwestern Medical Center; Estados Unidos
Fil: Kittler, Ralf. University of Texas. Southwestern Medical Center; Estados Unidos
Fil: Wistuba, Ignacio I.. University of Texas; Estados Unidos
Fil: Minna, John D.. University of Texas. Southwestern Medical Center; Estados Unidos
Fil: Martinez, Elisabeth D.. University of Texas. Southwestern Medical Center; Estados Unidos
Materia: NSCLCS
JIB-04
KDM
DRUG RESISTANCE
LUNG CANCER
Nivel de accesibilidad: acceso abierto
Condiciones de uso: https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
Institución: Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador: oai:ri.conicet.gov.ar:11336/45113

Acceder

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network_acronym_str	CONICETDig
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network_name_str	CONICET Digital (CONICET)
spelling	Taxane-Platin-Resistant Lung Cancers Co-develop Hypersensitivity to JumonjiC Demethylase InhibitorsDalvi, Maithili P.Wang, LeiZhong, RuiKollipara, Rahul K.Park, HyunsilBayo Fina, Juan MiguelYenerall, PaulZhou, YunyunTimmons, Brenda C.Rodriguez Canales, JaimeBehrens, CarmenMino, BarbaraVillalobos, PamelaParra, Edwin R.Suraokar, MilindPataer, AparSwisher, Stephen G.Kalhor, NedaBhanu, Natarajan V.Garcia, Benjamin A.Heymach, John V.Coombes, KevinXie, YangGirard, LucGazdar, Adi F.Kittler, RalfWistuba, Ignacio I.Minna, John D.Martinez, Elisabeth D.NSCLCSJIB-04KDMDRUG RESISTANCELUNG CANCERhttps://purl.org/becyt/ford/3.4https://purl.org/becyt/ford/3Although non-small cell lung cancer (NSCLC) patients benefit from standard taxane-platin chemotherapy, many relapse, developing drug resistance. We established preclinical taxane-platin-chemoresistance models and identified a 35-gene resistance signature, which was associated with poor recurrence-free survival in neoadjuvant-treated NSCLC patients and included upregulation of the JumonjiC lysine demethylase KDM3B. In fact, multi-drug-resistant cells progressively increased the expression of many JumonjiC demethylases, had altered histone methylation, and, importantly, showed hypersensitivity to JumonjiC inhibitors in vitro and in vivo. Increasing taxane-platin resistance in progressive cell line series was accompanied by progressive sensitization to JIB-04 and GSK-J4. These JumonjiC inhibitors partly reversed deregulated transcriptional programs, prevented the emergence of drug-tolerant colonies from chemo-naive cells, and synergized with standard chemotherapy in vitro and in vivo. Our findings reveal JumonjiC inhibitors as promising therapies for targeting taxane-platin-chemoresistant NSCLCs.Fil: Dalvi, Maithili P.. University of Texas. Southwestern Medical Center; Estados UnidosFil: Wang, Lei. University of Texas. Southwestern Medical Center; Estados UnidosFil: Zhong, Rui. University of Texas. Southwestern Medical Center; Estados UnidosFil: Kollipara, Rahul K.. University of Texas. Southwestern Medical Center; Estados UnidosFil: Park, Hyunsil. University of Texas. Southwestern Medical Center; Estados UnidosFil: Bayo Fina, Juan Miguel. University of Texas. Southwestern Medical Center; Estados Unidos. Universidad Austral. Facultad de Ciencias Biomédicas. Instituto de Investigaciones en Medicina Traslacional. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Medicina Traslacional; ArgentinaFil: Yenerall, Paul. University of Texas. Southwestern Medical Center; Estados UnidosFil: Zhou, Yunyun. University of Texas. Southwestern Medical Center; Estados UnidosFil: Timmons, Brenda C.. University of Texas. Southwestern Medical Center; Estados UnidosFil: Rodriguez Canales, Jaime. University of Texas; Estados UnidosFil: Behrens, Carmen. Md Anderson Cancer Center; Estados UnidosFil: Mino, Barbara. University of Texas; Estados UnidosFil: Villalobos, Pamela. University of Texas; Estados UnidosFil: Parra, Edwin R.. University of Texas; Estados UnidosFil: Suraokar, Milind. University of Texas; Estados UnidosFil: Pataer, Apar. University of Texas; Estados UnidosFil: Swisher, Stephen G.. University of Texas; Estados UnidosFil: Kalhor, Neda. University of Texas; Estados UnidosFil: Bhanu, Natarajan V.. University of Pennsylvania; Estados UnidosFil: Garcia, Benjamin A.. University of Pennsylvania; Estados UnidosFil: Heymach, John V.. University of Texas; Estados UnidosFil: Coombes, Kevin. University of Texas; Estados UnidosFil: Xie, Yang. University of Texas. Southwestern Medical Center; Estados UnidosFil: Girard, Luc. University of Texas. Southwestern Medical Center; Estados UnidosFil: Gazdar, Adi F.. University of Texas. Southwestern Medical Center; Estados UnidosFil: Kittler, Ralf. University of Texas. Southwestern Medical Center; Estados UnidosFil: Wistuba, Ignacio I.. University of Texas; Estados UnidosFil: Minna, John D.. University of Texas. Southwestern Medical Center; Estados UnidosFil: Martinez, Elisabeth D.. University of Texas. Southwestern Medical Center; Estados UnidosElsevier2017-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/45113Dalvi, Maithili P.; Wang, Lei; Zhong, Rui; Kollipara, Rahul K.; Park, Hyunsil; et al.; Taxane-Platin-Resistant Lung Cancers Co-develop Hypersensitivity to JumonjiC Demethylase Inhibitors; Elsevier; Cell Reports; 19; 8; 5-2017; 1669-16842211-1247CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S2211124717306071info:eu-repo/semantics/altIdentifier/doi/10.1016/j.celrep.2017.04.077info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-11-26T08:57:17Zoai:ri.conicet.gov.ar:11336/45113instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-11-26 08:57:18.237CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv	Taxane-Platin-Resistant Lung Cancers Co-develop Hypersensitivity to JumonjiC Demethylase Inhibitors
title	Taxane-Platin-Resistant Lung Cancers Co-develop Hypersensitivity to JumonjiC Demethylase Inhibitors
spellingShingle	Taxane-Platin-Resistant Lung Cancers Co-develop Hypersensitivity to JumonjiC Demethylase Inhibitors Dalvi, Maithili P. NSCLCS JIB-04 KDM DRUG RESISTANCE LUNG CANCER
title_short	Taxane-Platin-Resistant Lung Cancers Co-develop Hypersensitivity to JumonjiC Demethylase Inhibitors
title_full	Taxane-Platin-Resistant Lung Cancers Co-develop Hypersensitivity to JumonjiC Demethylase Inhibitors
title_fullStr	Taxane-Platin-Resistant Lung Cancers Co-develop Hypersensitivity to JumonjiC Demethylase Inhibitors
title_full_unstemmed	Taxane-Platin-Resistant Lung Cancers Co-develop Hypersensitivity to JumonjiC Demethylase Inhibitors
title_sort	Taxane-Platin-Resistant Lung Cancers Co-develop Hypersensitivity to JumonjiC Demethylase Inhibitors
dc.creator.none.fl_str_mv	Dalvi, Maithili P. Wang, Lei Zhong, Rui Kollipara, Rahul K. Park, Hyunsil Bayo Fina, Juan Miguel Yenerall, Paul Zhou, Yunyun Timmons, Brenda C. Rodriguez Canales, Jaime Behrens, Carmen Mino, Barbara Villalobos, Pamela Parra, Edwin R. Suraokar, Milind Pataer, Apar Swisher, Stephen G. Kalhor, Neda Bhanu, Natarajan V. Garcia, Benjamin A. Heymach, John V. Coombes, Kevin Xie, Yang Girard, Luc Gazdar, Adi F. Kittler, Ralf Wistuba, Ignacio I. Minna, John D. Martinez, Elisabeth D.
author	Dalvi, Maithili P.
author_facet	Dalvi, Maithili P. Wang, Lei Zhong, Rui Kollipara, Rahul K. Park, Hyunsil Bayo Fina, Juan Miguel Yenerall, Paul Zhou, Yunyun Timmons, Brenda C. Rodriguez Canales, Jaime Behrens, Carmen Mino, Barbara Villalobos, Pamela Parra, Edwin R. Suraokar, Milind Pataer, Apar Swisher, Stephen G. Kalhor, Neda Bhanu, Natarajan V. Garcia, Benjamin A. Heymach, John V. Coombes, Kevin Xie, Yang Girard, Luc Gazdar, Adi F. Kittler, Ralf Wistuba, Ignacio I. Minna, John D. Martinez, Elisabeth D.
author_role	author
author2	Wang, Lei Zhong, Rui Kollipara, Rahul K. Park, Hyunsil Bayo Fina, Juan Miguel Yenerall, Paul Zhou, Yunyun Timmons, Brenda C. Rodriguez Canales, Jaime Behrens, Carmen Mino, Barbara Villalobos, Pamela Parra, Edwin R. Suraokar, Milind Pataer, Apar Swisher, Stephen G. Kalhor, Neda Bhanu, Natarajan V. Garcia, Benjamin A. Heymach, John V. Coombes, Kevin Xie, Yang Girard, Luc Gazdar, Adi F. Kittler, Ralf Wistuba, Ignacio I. Minna, John D. Martinez, Elisabeth D.
author2_role	author author author author author author author author author author author author author author author author author author author author author author author author author author author author
dc.subject.none.fl_str_mv	NSCLCS JIB-04 KDM DRUG RESISTANCE LUNG CANCER
topic	NSCLCS JIB-04 KDM DRUG RESISTANCE LUNG CANCER
purl_subject.fl_str_mv	https://purl.org/becyt/ford/3.4 https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv	Although non-small cell lung cancer (NSCLC) patients benefit from standard taxane-platin chemotherapy, many relapse, developing drug resistance. We established preclinical taxane-platin-chemoresistance models and identified a 35-gene resistance signature, which was associated with poor recurrence-free survival in neoadjuvant-treated NSCLC patients and included upregulation of the JumonjiC lysine demethylase KDM3B. In fact, multi-drug-resistant cells progressively increased the expression of many JumonjiC demethylases, had altered histone methylation, and, importantly, showed hypersensitivity to JumonjiC inhibitors in vitro and in vivo. Increasing taxane-platin resistance in progressive cell line series was accompanied by progressive sensitization to JIB-04 and GSK-J4. These JumonjiC inhibitors partly reversed deregulated transcriptional programs, prevented the emergence of drug-tolerant colonies from chemo-naive cells, and synergized with standard chemotherapy in vitro and in vivo. Our findings reveal JumonjiC inhibitors as promising therapies for targeting taxane-platin-chemoresistant NSCLCs. Fil: Dalvi, Maithili P.. University of Texas. Southwestern Medical Center; Estados Unidos Fil: Wang, Lei. University of Texas. Southwestern Medical Center; Estados Unidos Fil: Zhong, Rui. University of Texas. Southwestern Medical Center; Estados Unidos Fil: Kollipara, Rahul K.. University of Texas. Southwestern Medical Center; Estados Unidos Fil: Park, Hyunsil. University of Texas. Southwestern Medical Center; Estados Unidos Fil: Bayo Fina, Juan Miguel. University of Texas. Southwestern Medical Center; Estados Unidos. Universidad Austral. Facultad de Ciencias Biomédicas. Instituto de Investigaciones en Medicina Traslacional. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Medicina Traslacional; Argentina Fil: Yenerall, Paul. University of Texas. Southwestern Medical Center; Estados Unidos Fil: Zhou, Yunyun. University of Texas. Southwestern Medical Center; Estados Unidos Fil: Timmons, Brenda C.. University of Texas. Southwestern Medical Center; Estados Unidos Fil: Rodriguez Canales, Jaime. University of Texas; Estados Unidos Fil: Behrens, Carmen. Md Anderson Cancer Center; Estados Unidos Fil: Mino, Barbara. University of Texas; Estados Unidos Fil: Villalobos, Pamela. University of Texas; Estados Unidos Fil: Parra, Edwin R.. University of Texas; Estados Unidos Fil: Suraokar, Milind. University of Texas; Estados Unidos Fil: Pataer, Apar. University of Texas; Estados Unidos Fil: Swisher, Stephen G.. University of Texas; Estados Unidos Fil: Kalhor, Neda. University of Texas; Estados Unidos Fil: Bhanu, Natarajan V.. University of Pennsylvania; Estados Unidos Fil: Garcia, Benjamin A.. University of Pennsylvania; Estados Unidos Fil: Heymach, John V.. University of Texas; Estados Unidos Fil: Coombes, Kevin. University of Texas; Estados Unidos Fil: Xie, Yang. University of Texas. Southwestern Medical Center; Estados Unidos Fil: Girard, Luc. University of Texas. Southwestern Medical Center; Estados Unidos Fil: Gazdar, Adi F.. University of Texas. Southwestern Medical Center; Estados Unidos Fil: Kittler, Ralf. University of Texas. Southwestern Medical Center; Estados Unidos Fil: Wistuba, Ignacio I.. University of Texas; Estados Unidos Fil: Minna, John D.. University of Texas. Southwestern Medical Center; Estados Unidos Fil: Martinez, Elisabeth D.. University of Texas. Southwestern Medical Center; Estados Unidos
description	Although non-small cell lung cancer (NSCLC) patients benefit from standard taxane-platin chemotherapy, many relapse, developing drug resistance. We established preclinical taxane-platin-chemoresistance models and identified a 35-gene resistance signature, which was associated with poor recurrence-free survival in neoadjuvant-treated NSCLC patients and included upregulation of the JumonjiC lysine demethylase KDM3B. In fact, multi-drug-resistant cells progressively increased the expression of many JumonjiC demethylases, had altered histone methylation, and, importantly, showed hypersensitivity to JumonjiC inhibitors in vitro and in vivo. Increasing taxane-platin resistance in progressive cell line series was accompanied by progressive sensitization to JIB-04 and GSK-J4. These JumonjiC inhibitors partly reversed deregulated transcriptional programs, prevented the emergence of drug-tolerant colonies from chemo-naive cells, and synergized with standard chemotherapy in vitro and in vivo. Our findings reveal JumonjiC inhibitors as promising therapies for targeting taxane-platin-chemoresistant NSCLCs.
publishDate	2017
dc.date.none.fl_str_mv	2017-05
dc.type.none.fl_str_mv	info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo
format	article
status_str	publishedVersion
dc.identifier.none.fl_str_mv	http://hdl.handle.net/11336/45113 Dalvi, Maithili P.; Wang, Lei; Zhong, Rui; Kollipara, Rahul K.; Park, Hyunsil; et al.; Taxane-Platin-Resistant Lung Cancers Co-develop Hypersensitivity to JumonjiC Demethylase Inhibitors; Elsevier; Cell Reports; 19; 8; 5-2017; 1669-1684 2211-1247 CONICET Digital CONICET
url	http://hdl.handle.net/11336/45113
identifier_str_mv	Dalvi, Maithili P.; Wang, Lei; Zhong, Rui; Kollipara, Rahul K.; Park, Hyunsil; et al.; Taxane-Platin-Resistant Lung Cancers Co-develop Hypersensitivity to JumonjiC Demethylase Inhibitors; Elsevier; Cell Reports; 19; 8; 5-2017; 1669-1684 2211-1247 CONICET Digital CONICET
dc.language.none.fl_str_mv	eng
language	eng
dc.relation.none.fl_str_mv	info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S2211124717306071 info:eu-repo/semantics/altIdentifier/doi/10.1016/j.celrep.2017.04.077
dc.rights.none.fl_str_mv	info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv	openAccess
rights_invalid_str_mv	https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv	application/pdf application/pdf
dc.publisher.none.fl_str_mv	Elsevier
publisher.none.fl_str_mv	Elsevier
dc.source.none.fl_str_mv	reponame:CONICET Digital (CONICET) instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str	CONICET Digital (CONICET)
collection	CONICET Digital (CONICET)
instname_str	Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv	CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv	dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score	13.011256

Taxane-Platin-Resistant Lung Cancers Co-develop Hypersensitivity to JumonjiC Demethylase Inhibitors

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