seminar 'Modelling pharmacogenomic interactions in cancer'
- 'Modelling pharmacogenomic interactions in cancer' by Prof. Lodewyk Wessels (Netherlands Cancer Institute, Amsterdam)
- February 7, 2017 (11:00)
- Jozef Schell seminar room, Technologiepark 927 - 9052 Zwijnaarde
- organized and hosted by Bioinformatics Institute Ghent
- please contact prof. Kathleen Marchal (kathleen.marchal@intec.ugent.be) if you are interested to meet and discuss with the speaker!
Abstract:
Systematic studies of cancer genomes are providing unprecedented insights into the molecular nature of human cancer. Using this information to guide the development and application of therapies in the clinic is challenging. Here we report how cancer-driving alterations identified in 11,289 tumors from 29 tissues (integrating mutations, copy-number alterations, methylation and gene expression) correlate with response to 265 compounds profiled in 1,001 human cancer cell-lines. We find that cell-lines faithfully recapitulate oncogenic aberrations identified in tumors, and that many of these associate with drug sensitivity or resistance. Logic-based modeling uncovers combinations of aberrations that specifically sensitize to drugs. For most drugs, combinations of mutations explain the drug response better than single mutations. Finally, projecting the identified markers back onto primary tumors captures their clinical relevance, in terms of prevalence in cancer patients. Our comprehensive analysis and associated datasets are rich resources to identify novel therapeutic options for selected cancer sub-populations.