Endoxifen exhibits anti-tumor activity in Her2+, tamox resistant tumors in lab

[Hopeful]

http://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=77548710-905e-49ad-bfaf-b6d7a0a96cde&cKey=fe7ddc97-923c-4007-8a7d-2931c687ad97&mKey=%7b507D311A-B6EC-436A-BD67-6D14ED39622C%7d

Hopeful

[Rich66]

Conclusions: We have demonstrated in both ER+ and ER+/HER2+ breast cancer cell lines that in contrast to Tam, endoxifen potently inhibits growth (both in vitro and in vivo), does not activate Erk1/2 signaling, and inhibits E₂-stimulated transcription of ER-regulated genes. Endoxifen exhibited potent antitumor activity in MCF7-HER2 xenografts refractory to Tam. These data support the ongoing NCI sponsored phase I studies of Z-endoxifen at Mayo Clinic and NCI.


Tamoxifen effectiveness is determined by ability of a body to turn it into/metabolize to endoxifen. It's a pro-drug for endoxifen.
http://www.sciencedaily.com/releases/2008/12/081211141838.htm

So I guess this article is suggesting some of the acquired resistance to TAM is due to a change in the metabolism/transformation of TAM...as opposed to resistance to TAM as a drug.