Novel Approaches to Breast Cancer Prevention and Inhibition of Metastases
Abstract
We combine fly genetics with haploid ES cell mutagenesis and in vivo mouse genetics to functionally characterize candidate breast cancer genes. Using mouse genetics we have progressed in defining the role of RANKL/RANK in sex hormone-driven breast cancer. Moreover, we have now provided strong evidence that inactivation of RANK also markedly delays and in some cases even prevents the development of BRCA1-mutant breast cancer. If correct this could lead to first cancer prevention trials in BRCA1 carriers using RANKL blockade. Using Drosophila modeling of Ras-driven transformation, we performed a near-genome wide screen for genes that control tumor progression. Using this system we have functionally identified multiple novel cancer genes that also play a role in breast cancer, e.g. the surface receptor TSPAN6. TPAN6 expression also correlates with prognosis in human breast cancer patients. Finally, we have progressed in generating a haploid ES cell library for all researchers and have already generated more than 46000 murine ES cell clones targeting ~ 11500 different genes. These can now been used to perform synthetic lethal drug screens or to uncover resistance to defined drugs. Thus, we continue on all proposed aims with the vision to provide rapid functional annotation of breast cancer genes and, in case or RANKL/RANK, to provide the experimental underpinning for clinical prevention trials with the vision to one day be able to prevent breast cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2014
- Accession Number
- ADA620323
Entities
People
- Josef Penninger
Organizations
- Institute of Molecular Biotechnology