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Targeting Palbociclib-Resistant Estrogen Receptor-Positive Breast Cancer Cells via Oncolytic Virotherapy
While clinical responses to palbociclib have been promising, metastatic breast cancer remains incurable due to the development of resistance. We generated estrogen receptor-positive (ER+) and ER-negative (ER−) cell line models and determined their permissiveness and cellular responses to an oncolyti...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6563125/ https://www.ncbi.nlm.nih.gov/pubmed/31100952 http://dx.doi.org/10.3390/cancers11050684 |
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author | Lypova, Nadiia Lanceta, Lilibeth Gipson, Alana Vega, Stephanie Garza-Morales, Rodolfo McMasters, Kelly M. Chesney, Jason Gomez-Gutierrez, Jorge G. Imbert-Fernandez, Yoannis |
author_facet | Lypova, Nadiia Lanceta, Lilibeth Gipson, Alana Vega, Stephanie Garza-Morales, Rodolfo McMasters, Kelly M. Chesney, Jason Gomez-Gutierrez, Jorge G. Imbert-Fernandez, Yoannis |
author_sort | Lypova, Nadiia |
collection | PubMed |
description | While clinical responses to palbociclib have been promising, metastatic breast cancer remains incurable due to the development of resistance. We generated estrogen receptor-positive (ER+) and ER-negative (ER−) cell line models and determined their permissiveness and cellular responses to an oncolytic adenovirus (OAd) known as Ad5/3-delta24. Analysis of ER+ and ER− palbociclib-resistant cells revealed two clearly distinguishable responses to the OAd. While ER+ palbociclib-resistant cells displayed a hypersensitive phenotype to the effects of the OAd, ER− palbociclib-resistant cells showed a resistant phenotype to the OAd. Hypersensitivity to the OAd in ER+ palbociclib-resistant cells correlated with a decrease in type I interferon (IFN) signaling, an increase in viral entry receptor expression, and an increase in cyclin E expression. OAd resistance in ER− palbociclib-resistant cells correlated with an increase in type I IFN signaling and a marked decrease in viral entry receptor. Using the OAd as monotherapy caused significant cytotoxicity to both ER+ and ER− palbociclib-sensitive cell lines. However, the addition of palbociclib increased the oncolytic activity of the OAd only in ER+ palbociclib-sensitive cells. Our studies provide a mechanistic base for a novel anti-cancer regimen composed of an OAd in combination with palbociclib for the treatment of ER+ breast cancer. |
format | Online Article Text |
id | pubmed-6563125 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-65631252019-06-17 Targeting Palbociclib-Resistant Estrogen Receptor-Positive Breast Cancer Cells via Oncolytic Virotherapy Lypova, Nadiia Lanceta, Lilibeth Gipson, Alana Vega, Stephanie Garza-Morales, Rodolfo McMasters, Kelly M. Chesney, Jason Gomez-Gutierrez, Jorge G. Imbert-Fernandez, Yoannis Cancers (Basel) Article While clinical responses to palbociclib have been promising, metastatic breast cancer remains incurable due to the development of resistance. We generated estrogen receptor-positive (ER+) and ER-negative (ER−) cell line models and determined their permissiveness and cellular responses to an oncolytic adenovirus (OAd) known as Ad5/3-delta24. Analysis of ER+ and ER− palbociclib-resistant cells revealed two clearly distinguishable responses to the OAd. While ER+ palbociclib-resistant cells displayed a hypersensitive phenotype to the effects of the OAd, ER− palbociclib-resistant cells showed a resistant phenotype to the OAd. Hypersensitivity to the OAd in ER+ palbociclib-resistant cells correlated with a decrease in type I interferon (IFN) signaling, an increase in viral entry receptor expression, and an increase in cyclin E expression. OAd resistance in ER− palbociclib-resistant cells correlated with an increase in type I IFN signaling and a marked decrease in viral entry receptor. Using the OAd as monotherapy caused significant cytotoxicity to both ER+ and ER− palbociclib-sensitive cell lines. However, the addition of palbociclib increased the oncolytic activity of the OAd only in ER+ palbociclib-sensitive cells. Our studies provide a mechanistic base for a novel anti-cancer regimen composed of an OAd in combination with palbociclib for the treatment of ER+ breast cancer. MDPI 2019-05-16 /pmc/articles/PMC6563125/ /pubmed/31100952 http://dx.doi.org/10.3390/cancers11050684 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Lypova, Nadiia Lanceta, Lilibeth Gipson, Alana Vega, Stephanie Garza-Morales, Rodolfo McMasters, Kelly M. Chesney, Jason Gomez-Gutierrez, Jorge G. Imbert-Fernandez, Yoannis Targeting Palbociclib-Resistant Estrogen Receptor-Positive Breast Cancer Cells via Oncolytic Virotherapy |
title | Targeting Palbociclib-Resistant Estrogen Receptor-Positive Breast Cancer Cells via Oncolytic Virotherapy |
title_full | Targeting Palbociclib-Resistant Estrogen Receptor-Positive Breast Cancer Cells via Oncolytic Virotherapy |
title_fullStr | Targeting Palbociclib-Resistant Estrogen Receptor-Positive Breast Cancer Cells via Oncolytic Virotherapy |
title_full_unstemmed | Targeting Palbociclib-Resistant Estrogen Receptor-Positive Breast Cancer Cells via Oncolytic Virotherapy |
title_short | Targeting Palbociclib-Resistant Estrogen Receptor-Positive Breast Cancer Cells via Oncolytic Virotherapy |
title_sort | targeting palbociclib-resistant estrogen receptor-positive breast cancer cells via oncolytic virotherapy |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6563125/ https://www.ncbi.nlm.nih.gov/pubmed/31100952 http://dx.doi.org/10.3390/cancers11050684 |
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