Phosphorylated hsp90 alfa as predictive and prognostic biomarker in tumors from patients treated with platinum analogs

Autores
Cuello Carrión, Fernando Darío; Semino, S.; Ibarra, J.; González, L.; García, M. B.; Vargas Roig, Laura Maria; Nadin, Silvia Beatriz
Año de publicación
2019
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
The heat shock protein HSP90α is a ubiquitous molecular chaperone specially required for cancer cells as it chaperones proteins involved in oncogenesis, making it an attractive target for anticancer therapy. Phosphorylated HSP90α (P-HSP90α) on the threonine 7 (Thr-7) accumulates at the sites of DNA damage, involving this protein in DNA damage response. In addition, the basal level of P-HSP90α has been proposed as a surrogate biomarker for genetic instability in tumor cells. Platinum analogs (cisplatin, carboplatin) that are widely used for the treatment of many solid tumors damage DNA by forming covalent adducts. Platinum-DNA adducts are bulky lesions that interfere with DNA replication machinery, resulting in the formation of DNA double strand breaks. These lesions can lead to genomic instability and cell death. Unfortunately, the development of resistance to platinum-based agents may limit efficacy of the chemotherapy. Thus, it remains a need for biomarkers of cisplatin-response and prognosis for cancer patients. Our aim was to determine the predictive and prognostic ability of P-HSP90α in primary tumors from cancer patients who received platinum-based chemotherapy (cisplatin/carboplatin). P-HSP90α expression was determined by immunohistochemistry in paraffin-embedded tumor tissues from 51 cancer patients before chemotherapy, with a mean follow-up of 19.2 months. The expression of the protein was evaluated according to a staining intensity score and proportion of positive tumor cells. Clinical response was assessed after the third cycle of chemotherapy. Disease-free (DFS) and overall survival (OS) were periodically determined. Patients with complete clinical response or partial response to chemotherapy showed nuclear expression of P-HSP90α in contrast with tumors from patients with stable disease or progressive disease (P<0.01). In addition, patients with high cytoplasmic proportion of P-HSP90α had a significantly worse OS (P<0.05). No statistically significant relationship was found between P-HSP90α expression and DFS. Our preliminary results provide evidence that P-HSP90α could be a potentially valuable biomarker in predicting response to platinum-based chemotherapy and, may also be useful for defining the prognosis of the disease.
Fil: Cuello Carrión, Fernando Darío. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
Fil: Semino, S.. Hospital Universitario Mendoza; Argentina
Fil: Ibarra, J.. Centro Oncológico de Integración Regional; Argentina
Fil: González, L.. Centro Oncológico de Integración Regional; Argentina
Fil: García, M. B.. Centro Oncológico de Integración Regional; Argentina
Fil: Vargas Roig, Laura Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
Fil: Nadin, Silvia Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
XXXVII Reunión Científica Anual de la Sociedad de Biología de Cuyo
San Luis
Argentina
Sociedad de Biología de Cuyo
Materia
HSP90ALFA
PREDICTIVE BIOMARKER
PROGNOSTIC BIOMARKER
CANCER PATIENTS
PLATINUM ANALOGS
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:11336/211195
Acceder
id CONICETDig_e0d2702e1e6c1c114a2432ee6c052bdf
oai_identifier_str oai:ri.conicet.gov.ar:11336/211195
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Phosphorylated hsp90 alfa as predictive and prognostic biomarker in tumors from patients treated with platinum analogsCuello Carrión, Fernando DaríoSemino, S.Ibarra, J.González, L.García, M. B.Vargas Roig, Laura MariaNadin, Silvia BeatrizHSP90ALFAPREDICTIVE BIOMARKERPROGNOSTIC BIOMARKERCANCER PATIENTSPLATINUM ANALOGShttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3The heat shock protein HSP90α is a ubiquitous molecular chaperone specially required for cancer cells as it chaperones proteins involved in oncogenesis, making it an attractive target for anticancer therapy. Phosphorylated HSP90α (P-HSP90α) on the threonine 7 (Thr-7) accumulates at the sites of DNA damage, involving this protein in DNA damage response. In addition, the basal level of P-HSP90α has been proposed as a surrogate biomarker for genetic instability in tumor cells. Platinum analogs (cisplatin, carboplatin) that are widely used for the treatment of many solid tumors damage DNA by forming covalent adducts. Platinum-DNA adducts are bulky lesions that interfere with DNA replication machinery, resulting in the formation of DNA double strand breaks. These lesions can lead to genomic instability and cell death. Unfortunately, the development of resistance to platinum-based agents may limit efficacy of the chemotherapy. Thus, it remains a need for biomarkers of cisplatin-response and prognosis for cancer patients. Our aim was to determine the predictive and prognostic ability of P-HSP90α in primary tumors from cancer patients who received platinum-based chemotherapy (cisplatin/carboplatin). P-HSP90α expression was determined by immunohistochemistry in paraffin-embedded tumor tissues from 51 cancer patients before chemotherapy, with a mean follow-up of 19.2 months. The expression of the protein was evaluated according to a staining intensity score and proportion of positive tumor cells. Clinical response was assessed after the third cycle of chemotherapy. Disease-free (DFS) and overall survival (OS) were periodically determined. Patients with complete clinical response or partial response to chemotherapy showed nuclear expression of P-HSP90α in contrast with tumors from patients with stable disease or progressive disease (P<0.01). In addition, patients with high cytoplasmic proportion of P-HSP90α had a significantly worse OS (P<0.05). No statistically significant relationship was found between P-HSP90α expression and DFS. Our preliminary results provide evidence that P-HSP90α could be a potentially valuable biomarker in predicting response to platinum-based chemotherapy and, may also be useful for defining the prognosis of the disease.Fil: Cuello Carrión, Fernando Darío. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Semino, S.. Hospital Universitario Mendoza; ArgentinaFil: Ibarra, J.. Centro Oncológico de Integración Regional; ArgentinaFil: González, L.. Centro Oncológico de Integración Regional; ArgentinaFil: García, M. B.. Centro Oncológico de Integración Regional; ArgentinaFil: Vargas Roig, Laura Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Nadin, Silvia Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaXXXVII Reunión Científica Anual de la Sociedad de Biología de CuyoSan LuisArgentinaSociedad de Biología de CuyoSociedad de Biología de Cuyo2019info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectReuniónBookhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/211195Phosphorylated hsp90 alfa as predictive and prognostic biomarker in tumors from patients treated with platinum analogs; XXXVII Reunión Científica Anual de la Sociedad de Biología de Cuyo; San Luis; Argentina; 2019; 39-39CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://sbcuyo.org.ar/reuniones-anuales-anteriores/Nacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:53:48Zoai:ri.conicet.gov.ar:11336/211195instacron: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:34982025-09-03 09:53:48.519CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Phosphorylated hsp90 alfa as predictive and prognostic biomarker in tumors from patients treated with platinum analogs
title Phosphorylated hsp90 alfa as predictive and prognostic biomarker in tumors from patients treated with platinum analogs
spellingShingle Phosphorylated hsp90 alfa as predictive and prognostic biomarker in tumors from patients treated with platinum analogs
Cuello Carrión, Fernando Darío
HSP90ALFA
PREDICTIVE BIOMARKER
PROGNOSTIC BIOMARKER
CANCER PATIENTS
PLATINUM ANALOGS
title_short Phosphorylated hsp90 alfa as predictive and prognostic biomarker in tumors from patients treated with platinum analogs
title_full Phosphorylated hsp90 alfa as predictive and prognostic biomarker in tumors from patients treated with platinum analogs
title_fullStr Phosphorylated hsp90 alfa as predictive and prognostic biomarker in tumors from patients treated with platinum analogs
title_full_unstemmed Phosphorylated hsp90 alfa as predictive and prognostic biomarker in tumors from patients treated with platinum analogs
title_sort Phosphorylated hsp90 alfa as predictive and prognostic biomarker in tumors from patients treated with platinum analogs
dc.creator.none.fl_str_mv Cuello Carrión, Fernando Darío
Semino, S.
Ibarra, J.
González, L.
García, M. B.
Vargas Roig, Laura Maria
Nadin, Silvia Beatriz
author Cuello Carrión, Fernando Darío
author_facet Cuello Carrión, Fernando Darío
Semino, S.
Ibarra, J.
González, L.
García, M. B.
Vargas Roig, Laura Maria
Nadin, Silvia Beatriz
author_role author
author2 Semino, S.
Ibarra, J.
González, L.
García, M. B.
Vargas Roig, Laura Maria
Nadin, Silvia Beatriz
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv HSP90ALFA
PREDICTIVE BIOMARKER
PROGNOSTIC BIOMARKER
CANCER PATIENTS
PLATINUM ANALOGS
topic HSP90ALFA
PREDICTIVE BIOMARKER
PROGNOSTIC BIOMARKER
CANCER PATIENTS
PLATINUM ANALOGS
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv The heat shock protein HSP90α is a ubiquitous molecular chaperone specially required for cancer cells as it chaperones proteins involved in oncogenesis, making it an attractive target for anticancer therapy. Phosphorylated HSP90α (P-HSP90α) on the threonine 7 (Thr-7) accumulates at the sites of DNA damage, involving this protein in DNA damage response. In addition, the basal level of P-HSP90α has been proposed as a surrogate biomarker for genetic instability in tumor cells. Platinum analogs (cisplatin, carboplatin) that are widely used for the treatment of many solid tumors damage DNA by forming covalent adducts. Platinum-DNA adducts are bulky lesions that interfere with DNA replication machinery, resulting in the formation of DNA double strand breaks. These lesions can lead to genomic instability and cell death. Unfortunately, the development of resistance to platinum-based agents may limit efficacy of the chemotherapy. Thus, it remains a need for biomarkers of cisplatin-response and prognosis for cancer patients. Our aim was to determine the predictive and prognostic ability of P-HSP90α in primary tumors from cancer patients who received platinum-based chemotherapy (cisplatin/carboplatin). P-HSP90α expression was determined by immunohistochemistry in paraffin-embedded tumor tissues from 51 cancer patients before chemotherapy, with a mean follow-up of 19.2 months. The expression of the protein was evaluated according to a staining intensity score and proportion of positive tumor cells. Clinical response was assessed after the third cycle of chemotherapy. Disease-free (DFS) and overall survival (OS) were periodically determined. Patients with complete clinical response or partial response to chemotherapy showed nuclear expression of P-HSP90α in contrast with tumors from patients with stable disease or progressive disease (P<0.01). In addition, patients with high cytoplasmic proportion of P-HSP90α had a significantly worse OS (P<0.05). No statistically significant relationship was found between P-HSP90α expression and DFS. Our preliminary results provide evidence that P-HSP90α could be a potentially valuable biomarker in predicting response to platinum-based chemotherapy and, may also be useful for defining the prognosis of the disease.
Fil: Cuello Carrión, Fernando Darío. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
Fil: Semino, S.. Hospital Universitario Mendoza; Argentina
Fil: Ibarra, J.. Centro Oncológico de Integración Regional; Argentina
Fil: González, L.. Centro Oncológico de Integración Regional; Argentina
Fil: García, M. B.. Centro Oncológico de Integración Regional; Argentina
Fil: Vargas Roig, Laura Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
Fil: Nadin, Silvia Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
XXXVII Reunión Científica Anual de la Sociedad de Biología de Cuyo
San Luis
Argentina
Sociedad de Biología de Cuyo
description The heat shock protein HSP90α is a ubiquitous molecular chaperone specially required for cancer cells as it chaperones proteins involved in oncogenesis, making it an attractive target for anticancer therapy. Phosphorylated HSP90α (P-HSP90α) on the threonine 7 (Thr-7) accumulates at the sites of DNA damage, involving this protein in DNA damage response. In addition, the basal level of P-HSP90α has been proposed as a surrogate biomarker for genetic instability in tumor cells. Platinum analogs (cisplatin, carboplatin) that are widely used for the treatment of many solid tumors damage DNA by forming covalent adducts. Platinum-DNA adducts are bulky lesions that interfere with DNA replication machinery, resulting in the formation of DNA double strand breaks. These lesions can lead to genomic instability and cell death. Unfortunately, the development of resistance to platinum-based agents may limit efficacy of the chemotherapy. Thus, it remains a need for biomarkers of cisplatin-response and prognosis for cancer patients. Our aim was to determine the predictive and prognostic ability of P-HSP90α in primary tumors from cancer patients who received platinum-based chemotherapy (cisplatin/carboplatin). P-HSP90α expression was determined by immunohistochemistry in paraffin-embedded tumor tissues from 51 cancer patients before chemotherapy, with a mean follow-up of 19.2 months. The expression of the protein was evaluated according to a staining intensity score and proportion of positive tumor cells. Clinical response was assessed after the third cycle of chemotherapy. Disease-free (DFS) and overall survival (OS) were periodically determined. Patients with complete clinical response or partial response to chemotherapy showed nuclear expression of P-HSP90α in contrast with tumors from patients with stable disease or progressive disease (P<0.01). In addition, patients with high cytoplasmic proportion of P-HSP90α had a significantly worse OS (P<0.05). No statistically significant relationship was found between P-HSP90α expression and DFS. Our preliminary results provide evidence that P-HSP90α could be a potentially valuable biomarker in predicting response to platinum-based chemotherapy and, may also be useful for defining the prognosis of the disease.
publishDate 2019
dc.date.none.fl_str_mv 2019
dc.type.none.fl_str_mv info:eu-repo/semantics/publishedVersion
info:eu-repo/semantics/conferenceObject
Reunión
Book
http://purl.org/coar/resource_type/c_5794
info:ar-repo/semantics/documentoDeConferencia
status_str publishedVersion
format conferenceObject
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/211195
Phosphorylated hsp90 alfa as predictive and prognostic biomarker in tumors from patients treated with platinum analogs; XXXVII Reunión Científica Anual de la Sociedad de Biología de Cuyo; San Luis; Argentina; 2019; 39-39
CONICET Digital
CONICET
url http://hdl.handle.net/11336/211195
identifier_str_mv Phosphorylated hsp90 alfa as predictive and prognostic biomarker in tumors from patients treated with platinum analogs; XXXVII Reunión Científica Anual de la Sociedad de Biología de Cuyo; San Luis; Argentina; 2019; 39-39
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://sbcuyo.org.ar/reuniones-anuales-anteriores/
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.coverage.none.fl_str_mv Nacional
dc.publisher.none.fl_str_mv Sociedad de Biología de Cuyo
publisher.none.fl_str_mv Sociedad de Biología de Cuyo
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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