Monday 07 December 2009, 23:45

Endoxifen: new hope for breast cancer treatment

Comparison between tamoxifen and its active metabolite endoxifen

Endoxifen: new hope for breast cancer treatment

Tamoxifen is a “selective estrogen receptor modulator” (SERM), largely used for the treatment of hormone-positive breast cancer. It reduces both the mortality rate in women with early breast cancer, as well as cancer recurrence after surgical treatment. However not all women respond to treatment with tamoxifen.


Tamoxifen is a “pro-drug”: it must be converted in its active form by the human body before it can perform its functions. The liver enzyme responsible for the conversion of tamoxifen into its active metabolite (endoxifen) is coded by the polymorphic gene CYP2D6. This enzyme is present in different forms in different people and some people may lack it entirely. That’s why not all women respond to treatment with tamoxifen: women with CYP2D6 variations (called “poor metabolizers”) metabolize levels of tamoxifen too low to prevent breast cancer recurrence.


In order to solve this inconvenient, research is now moving toward the study of endoxifen as an alternative drug to its parent tamoxifen. Endoxifen is the active metabolite produced by the enzymatic conversion of tamoxifen in the human body. Not only endoxifen is about 100 times more potent than tamoxifen itself, but it also acts through a completely different mechanism.


Tamoxifen is a SERM: it diffuses into the target cell, binds to estrogen receptor and translocates into the cell’s nucleus where it modulates the expression of a variety of specific genes. By contrast, after diffusion into the target cell, endoxifen causes the partial degradation of estrogen receptor and is responsible for the regulation of a set of genes different from that regulated by tamoxifen.


Research is now attempting to develop endoxifen as a drug. The hope is to develop a drug more potent and effective than tamoxifen and suitable for all women regardless of their genetic makeup.


By Chiara De Carli

Category: Pharmacy

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