Palbociclib and Fulvestrant Act in Synergy to Modulate Central Carbon Metabolism in Breast Cancer Cells

Metabolites

卷:9

Yuping Cai¹  NicholasJ.W. Rattray¹  David Shields²  Zhou Zhu²  ValeriaR. Fantin²  NathanV. Lee²  Todd VanArsdale²  Anthony Mazurek²  Stephen Dann²  Gary Siuzdak³  Amelia Palermo³  CarolineH. Johnson³  LinhT. Hoang³  Benedikt Warth³ 

[1] Department of Environmental Health Sciences, Yale School of Public Health, Yale University, New Haven, CT 06511, USA;

[2] Oncology Research, Pfizer Worldwide Research and Development, San Diego, CA 92121, USA;

[3] The Scripps Research Institute, Scripps Center for Metabolomics and Mass Spectrometry, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA;

关键词: combination drug therapy;    breast cancer;    multi-omics;    metabolomics;    RNA-seq;    XCMS Online;   

DOI  :  10.3390/metabo9010007

来源: DOAJ

【 摘 要 】

The aims of this study were to determine whether combination chemotherapeutics exhibit a synergistic effect on breast cancer cell metabolism. Palbociclib, is a selective inhibitor of cyclin-dependent kinases 4 and 6, and when patients are treated in combination with fulvestrant, an estrogen receptor antagonist, they have improved progression-free survival. The mechanisms for this survival advantage are not known. Therefore, we analyzed metabolic and transcriptomic changes in MCF-7 cells following single and combination chemotherapy to determine whether selective metabolic pathways are targeted during these different modes of treatment. 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 also highlights the power of merging high-dimensional datasets to unravel mechanisms involved in cancer metabolism and therapy.

【 授权许可】

Unknown