%0 Journal Article
%T Targeting Palbociclib-Resistant Estrogen Receptor-Positive Breast Cancer Cells via Oncolytic Virotherapy
%A Alana Gipson
%A Jason Chesney
%A Jorge G. Gomez-Gutierrez
%A Kelly M. McMasters
%A Lilibeth Lanceta
%A Nadiia Lypova
%A Rodolfo Garza-Morales
%A Stephanie Vega
%A Yoannis Imbert-Fernandez
%J Archive of "Cancers".
%D 2019
%R 10.3390/cancers11050684
%X 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
%K palbociclib
%K estrogen receptor
%K oncolytic adenovirus
%K breast cancer
%K virotherapy
%K CDK4/6
%K CDK4/6 inhibitors
%K therapy resistance
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6563125/