SUMMARY

During 2014 our research has advanced the understanding of mechanisms of sensitivity and resistance to targeted therapy in breast cancer, with two main areas of focus: the blockade of the PI3K-pathway as well as therapies targeting homologous recombination deficiency. Our ultimate aim is to provide hypothesisbased strategies to combine targeted therapy and, in so doing, improve outcomes for patients. To address these questions, we have established novel patient tumorderived breast cancer models in vivo, in collaboration with VHIO’s Breast Cancer and Melanoma Group led by Javier Cortés. These preclinical models faithfully recapitulate the disease and have been extremely useful in the study of targeted therapy sensitivity and resistance

Highlights this year have included the identification of two mechanisms that lead to activation of mTORC1 signaling and impair sensitivity to PI3K inhibitors. This preclinical observation has been linked with limited activity of these agents in the clinic and proposes therapeutic combination strategies to improve the activity of this class of agents. We have also developed a panel of ten patient-derived tumor xenografts from BRCA1/2-germline patients and evaluated the activity of novel therapeutic strategies exploiting the homologous recombination deficiency.

PUBLICATIONS