tamoxifen+resistance+and+relation+to+27HC

Tamoxifen is a FDA approved drug that targets the estrogen receptors in breast tissue. It is only prescribed for estrogen receptor positive breast cancer, most of the time after adjuvant therapy. Tamoxifen, otherwise known as Nolvadex, is a SERM, or a selective estrogen receptor modulator. ER+ breast cancer cells are activated by estrogen binding to the cells estrogen receptors. Tamoxifen binds to the estrogen receptor before the estrogen has a chance to bond. This eliminates the possibility for estrogen to bind. Because the estrogen can’t bind, it can’t activate cell proliferation.

The studies mentioned in our section on 27HC and other gene expression studies have revealed a potential association between 27HC exposure and the development of a resistance to Tamoxifen. The issue is that tamoxifen exhibits robust antagonist activity, causing 27HC promoted tumor growth, even when tamoxifen is present (Nelson, et al. 2013). This can be seen in figure 1B. In this figure we can see that 27HC is still facilitating growth of cells with tamoxifen. For this study, researchers used [|MCF7 cells], cells that mimic ER positive breast cancer cells, as they are an estrogen dependent environment. With these cells, they tested how 27HC binding promoted growth compared to [|17B-estradiol] (E2), which is an estrogen like steroid that binds ER receptors very well. The findings from the test illustrated that 27HC promoted the most tumor volume increase. However, the worrying aspect is that mice who had taken tamoxifen did not show a much slower tumor growth rate. References:
 * 1) Nelson, E. R., S. E. Wardell, J. S. Jasper, S. Park, S. Suchindran, M. K. Howe, N. J. Carver, R. V. Pillai, P. M. Sullivan, V. Sondhi, M. Umetani, J. Geradts, and D. P. Mcdonnell. "27-Hydroxycholesterol Links Hypercholesterolemia and Breast Cancer Pathophysiology." Science 342.6162 (2013): 1094-098. Web.
 * 2) Umetani, Michihisa, and Philip W. Shaul. "27-Hydroxycholesterol: The First Identified Endogenous SERM." NIH (2011): 1-10. National Institute of Health. Web.

To navigate back to our Title page, Cholesterol as a Cancer Promoter, Click HERE. Matthew Perez and Erik Christensen