Christer Larsson

The aims of the project are 1) to identify and understand novel mechanisms regulating breast cancer cell death and 2) to identify molecular patterns of importance for the tumor biology and disease outcome. For 1) we specifically study mechanisms of Smac mimetics which are small molecules mimicking the effect of the pro-apoptotic protein Smac. Some breast cancer cells go into apoptosis when treated with Smac mimetics whereas other cells need an additional apoptosis trigger for Smac mimetics to be effective. We investigate determinants of Smac-responsiveness and ways to circumvent resistance to Smac mimetics. One goal is to identify factors that can provide information regarding the most optimal co-treatment to optimize Smac mimetic efficiency. We have also discovered that Smac mimetics can induce long-term changes in the breast cancer cell phenotype. The mechanisms of this effect and what determines whether such a change, rather than cell death, is induced will be analyzed. For 2) we in particular focus on the molecular pattern of stromal components of the tumor. We utilize public data as and molecular data generated within the SCANB project, a continuous collection of consecutive material of breast cancers operated in Southern Sweden. We have discovered that the molecular composition, more than the extent, of stroma and tumor immune/inflammatory response is of prognostic importance.