Targeting Palbociclib-Resistant Estrogen Receptor-Positive Breast Cancer Cells via Oncolytic Virotherapy.

Autor: Lypova N; Department of Medicine, School of Medicine, University of Louisville, Louisville, KY 40202, USA. nadiia.lypova@louisville.edu., Lanceta L; Department of Medicine, School of Medicine, University of Louisville, Louisville, KY 40202, USA. lilibeth.lanceta@louisville.edu., Gibson A; The Hiram C. Polk Jr., MD, Department of Surgery, School of Medicine, University of Louisville, Louisville, KY 40202, USA. alana.gipson@louisville.edu., Vega S; Department of Medicine, School of Medicine, University of Louisville, Louisville, KY 40202, USA. s0vega01@louisville.edu., Garza-Morales R; The Hiram C. Polk Jr., MD, Department of Surgery, School of Medicine, University of Louisville, Louisville, KY 40202, USA. rodolfo.garzamorales@louisville.edu., McMasters KM; The Hiram C. Polk Jr., MD, Department of Surgery, School of Medicine, University of Louisville, Louisville, KY 40202, USA. kelly.mcmasters@louisville.edu.; James Graham Brown Cancer Center, School of Medicine, University of Louisville, Louisville, KY 40202, USA. kelly.mcmasters@louisville.edu., Chesney J; Department of Medicine, School of Medicine, University of Louisville, Louisville, KY 40202, USA. jason.chesney@louisville.edu.; James Graham Brown Cancer Center, School of Medicine, University of Louisville, Louisville, KY 40202, USA. jason.chesney@louisville.edu., Gomez-Gutierrez JG; The Hiram C. Polk Jr., MD, Department of Surgery, School of Medicine, University of Louisville, Louisville, KY 40202, USA. jgguti01@louisville.edu.; James Graham Brown Cancer Center, School of Medicine, University of Louisville, Louisville, KY 40202, USA. jgguti01@louisville.edu., Imbert-Fernandez Y; Department of Medicine, School of Medicine, University of Louisville, Louisville, KY 40202, USA. yoannis.imbertfernandez@louisville.edu.; James Graham Brown Cancer Center, School of Medicine, University of Louisville, Louisville, KY 40202, USA. yoannis.imbertfernandez@louisville.edu.
Jazyk: angličtina
Zdroj: Cancers [Cancers (Basel)] 2019 May 16; Vol. 11 (5). Date of Electronic Publication: 2019 May 16.
DOI: 10.3390/cancers11050684
Abstrakt: 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.
Databáze: MEDLINE
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