학술논문
Endoxifen downregulates AKT phosphorylation through protein kinase C beta 1 inhibition in ERα+ breast cancer
Document Type
article
Author
Swaathi Jayaraman; Xinyan Wu; Krishna R. Kalari; Xiaojia Tang; Mary J. Kuffel; Elizabeth S. Bruinsma; Shahrzad Jalali; Kevin L. Peterson; Cristina Correia; Rachel A. Kudgus; Scott H. Kaufmann; Santosh Renuse; James N. Ingle; Joel M. Reid; Matthew M. Ames; Alan P. Fields; Matthew J. Schellenberg; John R. Hawse; Akhilesh Pandey; Matthew P. Goetz
Source
npj Breast Cancer, Vol 9, Iss 1, Pp 1-16 (2023)
Subject
Language
English
ISSN
2374-4677
Abstract
Abstract Endoxifen, a secondary tamoxifen metabolite, is a potent antiestrogen exhibiting estrogen receptor alpha (ERα) binding at nanomolar concentrations. Phase I/II clinical trials identified clinical activity of Z-endoxifen (ENDX), in endocrine-refractory metastatic breast cancer as well as ERα+ solid tumors, raising the possibility that ENDX may have a second, ERα-independent, mechanism of action. An unbiased mass spectrometry approach revealed that ENDX concentrations achieved clinically with direct ENDX administration (5 µM), but not low concentrations observed during tamoxifen treatment (