scholarly journals Metabolomics and Transcriptional Responses in Estrogen Receptor Positive Breast Cancer Cells

Author(s):  
Soma Mandal ◽  
Protiti Khan ◽  
Lin Li ◽  
James R.
2018 ◽  
Author(s):  
Benedikt Warth ◽  
Amelia Palermo ◽  
Nicholas J.W. Rattray ◽  
Nathan V Lee ◽  
Zhou Zhu ◽  
...  

SummaryPalbociclib, is a selective inhibitor of cyclin-dependent kinases 4 and 6 and used as a first-line treatment for patients with estrogen receptor positive breast cancer. It has been shown that patients have improved progression-free survival when treated in combination with fulvestrant, an estrogen receptor antagonist. However, the mechanisms for this survival advantage are not known. We sought to analyze metabolic and transcriptomic changes in MCF-7 adenocarcinoma breast cancer cells following single and combined treatments to determine if selective metabolic pathways are targeted during combination therapy. Our results showed that individually, the drugs caused metabolic disruption to the same metabolic pathways, however fulvestrant additionally attenuated the pentose phosphate pathway and the production of important coenzymes. A comprehensive effect was observed when the drugs were applied together, confirming the combinatory therapy′s synergism in the cell model. This study highlights the power of merging high-dimensional datasets to unravel mechanisms involved in cancer metabolism and therapy.Highlights○First study employing multi-omics to investigate combined therapy on breast cancer cells○Fulvestrant attenuates the pentose phosphate pathway and coenzyme production○Synergism of palbociclib and fulvestrant was confirmed in vitro○Altered key pathways have been identifiedeTOC BlurbJohnson et al. applied an innovative multi-omics approach to decipher metabolic pathways affected by single versus combination dosing of palbociclib and fulvestrant in estrogen receptor positive breast cancer. Key metabolites and genes were correlated within metabolic pathways and shown to be involved in the drugs′ synergism.


2019 ◽  
Vol 38 (3) ◽  
pp. 558-573
Author(s):  
Estefany Ingrid Medina-Reyes ◽  
Marco Antonio Mancera-Rodríguez ◽  
Norma Laura Delgado-Buenrostro ◽  
Adriana Moreno-Rodríguez ◽  
Juan Luis Bautista-Martínez ◽  
...  

Oncogene ◽  
2020 ◽  
Vol 39 (34) ◽  
pp. 5649-5662
Author(s):  
Johanna M. Buschhaus ◽  
Brock A. Humphries ◽  
Samantha S. Eckley ◽  
Tanner H. Robison ◽  
Alyssa C. Cutter ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document