Mechanistic insights into the pathogenesis of microtubule‐targeting agent‐induced peripheral neuropathy from pharmacogenetic and functional studies

Autores
Chua, Katherina C.; El Haj, Nura; Priotti, Josefina; Kroetz, Deanna L.
Año de publicación
2022
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Chemotherapy-induced peripheral neuropathy (CIPN) is a common dose-limiting toxicity that affects 30%-40% of patients undergoing cancer treatment. Although multiple mechanisms of chemotherapy-induced neurotoxicity have been described in preclinical models, these have not been translated into widely effective strategies for the prevention or treatment of CIPN. Predictive biomarkers to inform therapeutic approaches are also lacking. Recent studies have examined genetic risk factors associated with CIPN susceptibility. This review provides an overview of the clinical and pathologic features of CIPN and summarizes efforts to identify target pathways through genetic and functional studies. Structurally and mechanistically diverse chemotherapeutics are associated with CIPN; however, the current review is focused on microtubule-targeting agents since these are the focus of most pharmacogenetic association and functional studies of CIPN. Genome-wide pharmacogenetic association studies are useful tools to identify not only causative genes and genetic variants but also genetic networks implicated in drug response or toxicity and have been increasingly applied to investigations of CIPN. Induced pluripotent stem cell-derived models of human sensory neurons are especially useful to understand the mechanistic significance of genomic findings. Combined genetic and functional genomic efforts to understand CIPN hold great promise for developing therapeutic approaches for its prevention and treatment.
Fil: Chua, Katherina C.. University of California; Estados Unidos
Fil: El Haj, Nura. University of California; Estados Unidos
Fil: Priotti, Josefina. University of California; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina
Fil: Kroetz, Deanna L.. University of California; Estados Unidos
Materia
CHEMOTHERAPY-INDUCED PERIPHERAL NEUROPATHY
GENOME-WIDE ASSOCIATION STUDIES
INDUCED PLURIPOTENT STEM CELLS
MICROTUBULE-TARGETING AGENTS
SENSORY NEURONS
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/154331

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network_name_str CONICET Digital (CONICET)
spelling Mechanistic insights into the pathogenesis of microtubule‐targeting agent‐induced peripheral neuropathy from pharmacogenetic and functional studiesChua, Katherina C.El Haj, NuraPriotti, JosefinaKroetz, Deanna L.CHEMOTHERAPY-INDUCED PERIPHERAL NEUROPATHYGENOME-WIDE ASSOCIATION STUDIESINDUCED PLURIPOTENT STEM CELLSMICROTUBULE-TARGETING AGENTSSENSORY NEURONShttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Chemotherapy-induced peripheral neuropathy (CIPN) is a common dose-limiting toxicity that affects 30%-40% of patients undergoing cancer treatment. Although multiple mechanisms of chemotherapy-induced neurotoxicity have been described in preclinical models, these have not been translated into widely effective strategies for the prevention or treatment of CIPN. Predictive biomarkers to inform therapeutic approaches are also lacking. Recent studies have examined genetic risk factors associated with CIPN susceptibility. This review provides an overview of the clinical and pathologic features of CIPN and summarizes efforts to identify target pathways through genetic and functional studies. Structurally and mechanistically diverse chemotherapeutics are associated with CIPN; however, the current review is focused on microtubule-targeting agents since these are the focus of most pharmacogenetic association and functional studies of CIPN. Genome-wide pharmacogenetic association studies are useful tools to identify not only causative genes and genetic variants but also genetic networks implicated in drug response or toxicity and have been increasingly applied to investigations of CIPN. Induced pluripotent stem cell-derived models of human sensory neurons are especially useful to understand the mechanistic significance of genomic findings. Combined genetic and functional genomic efforts to understand CIPN hold great promise for developing therapeutic approaches for its prevention and treatment.Fil: Chua, Katherina C.. University of California; Estados UnidosFil: El Haj, Nura. University of California; Estados UnidosFil: Priotti, Josefina. University of California; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; ArgentinaFil: Kroetz, Deanna L.. University of California; Estados UnidosWiley Blackwell Publishing, Inc2022-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/154331Chua, Katherina C.; El Haj, Nura; Priotti, Josefina; Kroetz, Deanna L.; Mechanistic insights into the pathogenesis of microtubule‐targeting agent‐induced peripheral neuropathy from pharmacogenetic and functional studies; Wiley Blackwell Publishing, Inc; Basic & Clinical Pharmacology & Toxicology; 130; 1; 1-2022; 60-741742-78351742-7843CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/10.1111/bcpt.13654info:eu-repo/semantics/altIdentifier/doi/10.1111/bcpt.13654info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:39:09Zoai:ri.conicet.gov.ar:11336/154331instacron: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:34982025-09-29 10:39:09.59CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Mechanistic insights into the pathogenesis of microtubule‐targeting agent‐induced peripheral neuropathy from pharmacogenetic and functional studies
title Mechanistic insights into the pathogenesis of microtubule‐targeting agent‐induced peripheral neuropathy from pharmacogenetic and functional studies
spellingShingle Mechanistic insights into the pathogenesis of microtubule‐targeting agent‐induced peripheral neuropathy from pharmacogenetic and functional studies
Chua, Katherina C.
CHEMOTHERAPY-INDUCED PERIPHERAL NEUROPATHY
GENOME-WIDE ASSOCIATION STUDIES
INDUCED PLURIPOTENT STEM CELLS
MICROTUBULE-TARGETING AGENTS
SENSORY NEURONS
title_short Mechanistic insights into the pathogenesis of microtubule‐targeting agent‐induced peripheral neuropathy from pharmacogenetic and functional studies
title_full Mechanistic insights into the pathogenesis of microtubule‐targeting agent‐induced peripheral neuropathy from pharmacogenetic and functional studies
title_fullStr Mechanistic insights into the pathogenesis of microtubule‐targeting agent‐induced peripheral neuropathy from pharmacogenetic and functional studies
title_full_unstemmed Mechanistic insights into the pathogenesis of microtubule‐targeting agent‐induced peripheral neuropathy from pharmacogenetic and functional studies
title_sort Mechanistic insights into the pathogenesis of microtubule‐targeting agent‐induced peripheral neuropathy from pharmacogenetic and functional studies
dc.creator.none.fl_str_mv Chua, Katherina C.
El Haj, Nura
Priotti, Josefina
Kroetz, Deanna L.
author Chua, Katherina C.
author_facet Chua, Katherina C.
El Haj, Nura
Priotti, Josefina
Kroetz, Deanna L.
author_role author
author2 El Haj, Nura
Priotti, Josefina
Kroetz, Deanna L.
author2_role author
author
author
dc.subject.none.fl_str_mv CHEMOTHERAPY-INDUCED PERIPHERAL NEUROPATHY
GENOME-WIDE ASSOCIATION STUDIES
INDUCED PLURIPOTENT STEM CELLS
MICROTUBULE-TARGETING AGENTS
SENSORY NEURONS
topic CHEMOTHERAPY-INDUCED PERIPHERAL NEUROPATHY
GENOME-WIDE ASSOCIATION STUDIES
INDUCED PLURIPOTENT STEM CELLS
MICROTUBULE-TARGETING AGENTS
SENSORY NEURONS
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Chemotherapy-induced peripheral neuropathy (CIPN) is a common dose-limiting toxicity that affects 30%-40% of patients undergoing cancer treatment. Although multiple mechanisms of chemotherapy-induced neurotoxicity have been described in preclinical models, these have not been translated into widely effective strategies for the prevention or treatment of CIPN. Predictive biomarkers to inform therapeutic approaches are also lacking. Recent studies have examined genetic risk factors associated with CIPN susceptibility. This review provides an overview of the clinical and pathologic features of CIPN and summarizes efforts to identify target pathways through genetic and functional studies. Structurally and mechanistically diverse chemotherapeutics are associated with CIPN; however, the current review is focused on microtubule-targeting agents since these are the focus of most pharmacogenetic association and functional studies of CIPN. Genome-wide pharmacogenetic association studies are useful tools to identify not only causative genes and genetic variants but also genetic networks implicated in drug response or toxicity and have been increasingly applied to investigations of CIPN. Induced pluripotent stem cell-derived models of human sensory neurons are especially useful to understand the mechanistic significance of genomic findings. Combined genetic and functional genomic efforts to understand CIPN hold great promise for developing therapeutic approaches for its prevention and treatment.
Fil: Chua, Katherina C.. University of California; Estados Unidos
Fil: El Haj, Nura. University of California; Estados Unidos
Fil: Priotti, Josefina. University of California; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina
Fil: Kroetz, Deanna L.. University of California; Estados Unidos
description Chemotherapy-induced peripheral neuropathy (CIPN) is a common dose-limiting toxicity that affects 30%-40% of patients undergoing cancer treatment. Although multiple mechanisms of chemotherapy-induced neurotoxicity have been described in preclinical models, these have not been translated into widely effective strategies for the prevention or treatment of CIPN. Predictive biomarkers to inform therapeutic approaches are also lacking. Recent studies have examined genetic risk factors associated with CIPN susceptibility. This review provides an overview of the clinical and pathologic features of CIPN and summarizes efforts to identify target pathways through genetic and functional studies. Structurally and mechanistically diverse chemotherapeutics are associated with CIPN; however, the current review is focused on microtubule-targeting agents since these are the focus of most pharmacogenetic association and functional studies of CIPN. Genome-wide pharmacogenetic association studies are useful tools to identify not only causative genes and genetic variants but also genetic networks implicated in drug response or toxicity and have been increasingly applied to investigations of CIPN. Induced pluripotent stem cell-derived models of human sensory neurons are especially useful to understand the mechanistic significance of genomic findings. Combined genetic and functional genomic efforts to understand CIPN hold great promise for developing therapeutic approaches for its prevention and treatment.
publishDate 2022
dc.date.none.fl_str_mv 2022-01
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/11336/154331
Chua, Katherina C.; El Haj, Nura; Priotti, Josefina; Kroetz, Deanna L.; Mechanistic insights into the pathogenesis of microtubule‐targeting agent‐induced peripheral neuropathy from pharmacogenetic and functional studies; Wiley Blackwell Publishing, Inc; Basic & Clinical Pharmacology & Toxicology; 130; 1; 1-2022; 60-74
1742-7835
1742-7843
CONICET Digital
CONICET
url http://hdl.handle.net/11336/154331
identifier_str_mv Chua, Katherina C.; El Haj, Nura; Priotti, Josefina; Kroetz, Deanna L.; Mechanistic insights into the pathogenesis of microtubule‐targeting agent‐induced peripheral neuropathy from pharmacogenetic and functional studies; Wiley Blackwell Publishing, Inc; Basic & Clinical Pharmacology & Toxicology; 130; 1; 1-2022; 60-74
1742-7835
1742-7843
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://onlinelibrary.wiley.com/doi/10.1111/bcpt.13654
info:eu-repo/semantics/altIdentifier/doi/10.1111/bcpt.13654
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 Wiley Blackwell Publishing, Inc
publisher.none.fl_str_mv Wiley Blackwell Publishing, Inc
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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