Grant: Operating Grant

It is now well-known that most breast tumours are sensitive to estrogens, that is, these steroid hormones contribute to their growth. Inhibiting the synthesis of these molecules within the body of cancer patients has thus been explored as a means of fighting cancer. Among the present used drugs there are selective estrogen receptor modulators, such as tamoxifen. However, the existing products only give partial results, not to mention sometimes severe side effects, even for example promoting endometrial cancer. The aromatase inhibitors blocking partially estrogen synthesis gives better results, but not yet a complete therapy. We now intend to find new ways of blocking more generally the synthesis of estrogens, by deepening our understanding of how the body produces them through the action of enzymes that activate estrogens, such as estrone sulfatase and 17betahydroxysteroid dehydrogenases. We will notably experiment, in cancer cell lines and mice, a number of inhibitors able to block the action of these enzymes, in other words, able to deprive cancerous cells of active estrogens that stimulate their growth. We will identify the necessary combined use of the enzyme inhibitors. The efficacy of using a new selective estrogen receptor modulator Raloxifen alone, inhibitors of the most important enzymes proved above, or both of them, will be tested in animal models for breast cancer. In the end of this study, we will identify a combinatory therapy for different sub-types of breast cancer with varying enzyme expression profiles, for further pre-clinical studies.