By employing whole genome sequencing and RNA sequencing on a large number of clinical samples, we have now created a huge data set that allows us not only to discover new (genomic) biomarkers but also investigate resistance mechanisms with subsequent “wet lab” approaches. Examples are the role of KRAS mutants in chemotherapy resistance and the role antigen-presentation machinery in immune responses. Basic research findings can almost be immediately translated into small clinical studies. The Drug Rediscovery Protocol, in short the DRUP study, is now a brand name for defined off label use of approved drugs. In this multi-pharma (12 companies to date), multi-drug (27 drugs to date), multi-center (37 centers to date) study we have the ability to test multiple hypotheses.
We also invested a great deal of time and energy in obtaining paired biopsies from tumors such as (but not limited to) melanoma or lung patients treated with e.g. immunotherapy. This resource helps us to better understand the genomic evolution of tumors under treatment pressure.
Several other new and exciting avenues are currently explored. First, we are creating a catalogue of the microbiome and viruses present in metastases of solid tumors. We have >5000 tumor biopsies, whole genome sequenced, also with RNA sequencing data on the majority of samples and clinically annotated that are a unique resource to address questions related to the impact of the microbiome on outcome.
Secondly, we are now constructing a database by adding digital pathology and imaging data to be able to develop machine learning technologies and to determine whether these new technologies can contribute to a better patient selection for therapy.
Thirdly, in collaboration with the group of Bas van Steensel we are now examining the value of noncoding sequences.