Work Package 1: European Breast Cancer Model Platform (EBCM)
The goal of PREDECT WP1 is to generate robust, next generation in vitro models of breast cancer for target validation. These improved models will hopefully reproduce authentic tumor-host interactions, the contribution from microenvironment and represent intratumoral heterogeneity.
Genetically engineered mouse models and advanced intraductally orthotopic xenografts will provide materials for tissue slices, simple and complex co-cultures (with cancer associated fibroblasts) in 3D matrices, including options to scale and manipulate cultures under bioreactor conditions. All of the platforms will be interrogated and compared as TMAs from paraffin-fixed material, using multiplexed immunohistochemistry.
The models will be first evaluated with regards to viability, proliferation, the expression of stress proteins (such as those associated with hypoxia) and stromal cell components as well as for protein expression specific for oestrogen receptor positive (ER+) breast cancer. Treatments for relapse from estrogen antagonists remains an important medical need but, in addition, the choice of this pathology permits interrogation of signalling and transcription pathways in novel in vivo and in vitro models when they are perturbed by well established antihormal drugs. The resting and perturbed states, using estrogen antagonists, of the novel models will be compared with existing clinical data to establish their fidelity to reproduce the complexity of human cancer.
- Juha Klefström, U. Helsinki, Academic WP1 Leader
- Elizabeth Anderson, Boehringer Ingelheim, EFPIA WP1 Co-Leader
- Cathrin Brisken, EPFL
- Adam Nopora, ROCHE
- Catarina Brito, IBET
- Loredana Vesci, Sigma-Tau
- Matt Smalley, Cardiff U; Simon Barry, AstraZeneca
- Sylvia Grünewald, Bayer