Understanding the heterogeneity of pancreatic ductal adenocarcinoma

Autores
Iovanna, Juan Lucio; Fraunhoffer Navarro, Nicolas Alejandro; Urrutia, Raul; Dusetti, Nelson Javier
Año de publicación
2025
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive, treatment-resistant cancer characterized by extensive inter- and intra-tumoral heterogeneity. Although over 95 % of cases harbor KRAS mutations and commonly altered tumor suppressors like TP53, SMAD4, and CDKN2A, these genetic changes alone do not fully explain PDAC variability. We propose a paradigm shift: PDAC heterogeneity is not solely genetic but also shaped by epigenetic regulation and the tumor microenvironment. Traditional transcriptomic classifications define PDAC into fixed subtypes, primarily classical and basal-like, but we argue these are not static categories. Instead, PDAC phenotypes exist along a dynamic continuum influenced by stromal interactions and epigenetic cues. This model challenges the binary classification view. We show that transitions from classical to basal-like states are gradual and reversible, driven by tumor-stroma crosstalk and chromatin remodeling. Such plasticity underpins tumor adaptation, resistance, and progression. Embracing this dynamic framework offers novel therapeutic opportunities.
Fil: Iovanna, Juan Lucio. Inserm; Francia. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic; Argentina. Universidad Nacional Arturo Jauretche; Argentina
Fil: Fraunhoffer Navarro, Nicolas Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina
Fil: Urrutia, Raul. Medical College Of Wisconsin; Estados Unidos
Fil: Dusetti, Nelson Javier. Inserm; Francia
Materia
PANCREATIC CANCER
HETEROGENEITY
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/290929
Acceder
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spelling Understanding the heterogeneity of pancreatic ductal adenocarcinomaIovanna, Juan LucioFraunhoffer Navarro, Nicolas AlejandroUrrutia, RaulDusetti, Nelson JavierPANCREATIC CANCERHETEROGENEITYhttps://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive, treatment-resistant cancer characterized by extensive inter- and intra-tumoral heterogeneity. Although over 95 % of cases harbor KRAS mutations and commonly altered tumor suppressors like TP53, SMAD4, and CDKN2A, these genetic changes alone do not fully explain PDAC variability. We propose a paradigm shift: PDAC heterogeneity is not solely genetic but also shaped by epigenetic regulation and the tumor microenvironment. Traditional transcriptomic classifications define PDAC into fixed subtypes, primarily classical and basal-like, but we argue these are not static categories. Instead, PDAC phenotypes exist along a dynamic continuum influenced by stromal interactions and epigenetic cues. This model challenges the binary classification view. We show that transitions from classical to basal-like states are gradual and reversible, driven by tumor-stroma crosstalk and chromatin remodeling. Such plasticity underpins tumor adaptation, resistance, and progression. Embracing this dynamic framework offers novel therapeutic opportunities.Fil: Iovanna, Juan Lucio. Inserm; Francia. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic; Argentina. Universidad Nacional Arturo Jauretche; ArgentinaFil: Fraunhoffer Navarro, Nicolas Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Urrutia, Raul. Medical College Of Wisconsin; Estados UnidosFil: Dusetti, Nelson Javier. Inserm; FranciaElsevier2025-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/290929Iovanna, Juan Lucio; Fraunhoffer Navarro, Nicolas Alejandro; Urrutia, Raul; Dusetti, Nelson Javier; Understanding the heterogeneity of pancreatic ductal adenocarcinoma; Elsevier; Translational Oncology; 60; 10-2025; 1-101936-5233CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S1936523325002104?via%3Dihubinfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.tranon.2025.102479info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2026-08-25T14:43:44Zoai:ri.conicet.gov.ar:11336/290929instacron: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:34982026-08-25 14:43:44.346CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Understanding the heterogeneity of pancreatic ductal adenocarcinoma
title Understanding the heterogeneity of pancreatic ductal adenocarcinoma
spellingShingle Understanding the heterogeneity of pancreatic ductal adenocarcinoma
Iovanna, Juan Lucio
PANCREATIC CANCER
HETEROGENEITY
title_short Understanding the heterogeneity of pancreatic ductal adenocarcinoma
title_full Understanding the heterogeneity of pancreatic ductal adenocarcinoma
title_fullStr Understanding the heterogeneity of pancreatic ductal adenocarcinoma
title_full_unstemmed Understanding the heterogeneity of pancreatic ductal adenocarcinoma
title_sort Understanding the heterogeneity of pancreatic ductal adenocarcinoma
dc.creator.none.fl_str_mv Iovanna, Juan Lucio
Fraunhoffer Navarro, Nicolas Alejandro
Urrutia, Raul
Dusetti, Nelson Javier
author Iovanna, Juan Lucio
author_facet Iovanna, Juan Lucio
Fraunhoffer Navarro, Nicolas Alejandro
Urrutia, Raul
Dusetti, Nelson Javier
author_role author
author2 Fraunhoffer Navarro, Nicolas Alejandro
Urrutia, Raul
Dusetti, Nelson Javier
author2_role author
author
author
dc.subject.none.fl_str_mv PANCREATIC CANCER
HETEROGENEITY
topic PANCREATIC CANCER
HETEROGENEITY
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive, treatment-resistant cancer characterized by extensive inter- and intra-tumoral heterogeneity. Although over 95 % of cases harbor KRAS mutations and commonly altered tumor suppressors like TP53, SMAD4, and CDKN2A, these genetic changes alone do not fully explain PDAC variability. We propose a paradigm shift: PDAC heterogeneity is not solely genetic but also shaped by epigenetic regulation and the tumor microenvironment. Traditional transcriptomic classifications define PDAC into fixed subtypes, primarily classical and basal-like, but we argue these are not static categories. Instead, PDAC phenotypes exist along a dynamic continuum influenced by stromal interactions and epigenetic cues. This model challenges the binary classification view. We show that transitions from classical to basal-like states are gradual and reversible, driven by tumor-stroma crosstalk and chromatin remodeling. Such plasticity underpins tumor adaptation, resistance, and progression. Embracing this dynamic framework offers novel therapeutic opportunities.
Fil: Iovanna, Juan Lucio. Inserm; Francia. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic; Argentina. Universidad Nacional Arturo Jauretche; Argentina
Fil: Fraunhoffer Navarro, Nicolas Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina
Fil: Urrutia, Raul. Medical College Of Wisconsin; Estados Unidos
Fil: Dusetti, Nelson Javier. Inserm; Francia
description Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive, treatment-resistant cancer characterized by extensive inter- and intra-tumoral heterogeneity. Although over 95 % of cases harbor KRAS mutations and commonly altered tumor suppressors like TP53, SMAD4, and CDKN2A, these genetic changes alone do not fully explain PDAC variability. We propose a paradigm shift: PDAC heterogeneity is not solely genetic but also shaped by epigenetic regulation and the tumor microenvironment. Traditional transcriptomic classifications define PDAC into fixed subtypes, primarily classical and basal-like, but we argue these are not static categories. Instead, PDAC phenotypes exist along a dynamic continuum influenced by stromal interactions and epigenetic cues. This model challenges the binary classification view. We show that transitions from classical to basal-like states are gradual and reversible, driven by tumor-stroma crosstalk and chromatin remodeling. Such plasticity underpins tumor adaptation, resistance, and progression. Embracing this dynamic framework offers novel therapeutic opportunities.
publishDate 2025
dc.date.none.fl_str_mv 2025-10
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/11336/290929
Iovanna, Juan Lucio; Fraunhoffer Navarro, Nicolas Alejandro; Urrutia, Raul; Dusetti, Nelson Javier; Understanding the heterogeneity of pancreatic ductal adenocarcinoma; Elsevier; Translational Oncology; 60; 10-2025; 1-10
1936-5233
CONICET Digital
CONICET
url http://hdl.handle.net/11336/290929
identifier_str_mv Iovanna, Juan Lucio; Fraunhoffer Navarro, Nicolas Alejandro; Urrutia, Raul; Dusetti, Nelson Javier; Understanding the heterogeneity of pancreatic ductal adenocarcinoma; Elsevier; Translational Oncology; 60; 10-2025; 1-10
1936-5233
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/S1936523325002104?via%3Dihub
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.tranon.2025.102479
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/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 13.24418

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