Study of the deregulation of cholesterol metabolism in cancers: Toward new perspectives in breast cancer treatment and response to tamoxifen

• Applicant: Dr. Rabea Bartölke
• Subject Area: Gynaecology and Obstetrics ; Biochemistry ; Cell Biology
• Term: from 2016 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 325225985

Breast cancer is the most common female cancer. Recently, cholesterol metabolism has been implicated not only in the development of breast cancer, but also in the resistance to tamoxifen, one of the major drugs used for treatment of breast cancers. Current research has shown that certain metabolites of the cholesterol metabolic pathway promote, while others suppress breast cancer. The team of M. Poirot and S. Silvente-Poirot showed that deregulations along this pathway favor the accumulation of an oncometabolite with tumor-promoting activity in breast cancer and that its production can be inhibited by Tamoxifen. The enzyme generating this oncometabolite has recently been identified by the team. One important goal of this proposal is to study its catalytic properties towards the production of the oncometabolite, as well as its transcriptional (de)regulation in normal and cancer cells. In this way it should be possible to examine whether it may be targeted by novel anticancer therapies and used as a marker of response to tamoxifen. Using a mouse model of spontaneous breast cancer, the contribution of this metabolism on breast cancer development will be determined, and the influence of a diet rich in cholesterol to the production of this cholesterol-derived oncometabolite will be defined.

• DFG Programme: Research Fellowships
• International Connection: France
• Host: Dr. Sandrine Silvente-Poirot