Theme leader

Dr. M. Spaargaren

Theme members

Target & Therapy Discovery

Still many patients succumb from cancer despite application of invasive treatment protocols, and novel therapies are urgently awaited. Cancer arises by epigenetic and genetic changes in genes acting in cellular signaling pathways. In addition, signals from the microenvironment impact tumor behavior. The molecular catalogues of all human malignancies are rapidly becoming available. Current targeted treatment strategies mainly exploit the oncogene addiction concept, and meet limitations. Innovative therapeutic opportunities lie in exploiting synthetic and collateral lethality as well as the cross-talk between cancer cells and their microenvironment. Importantly, molecular differences between tumor cells and stromal components of individual patients require personalized treatment approaches, and limited treatment efficacy due to intratumoral heterogeneity and primary or acquired drug-resistance demands the development of novel strategies such as combination therapies.

In this research theme, novel drug targets are identified by descriptive genomics approaches, molecular and functional analysis of specific signaling pathways, but also by focused as well as unbiased genome-wide siRNA and CRISPR functional genomic screens. Chemical and biological inhibitors of candidate targets are tested in a preclinical setting employing cell lines, primary patient material, and xenografted as well as transgenic animal models. In addition, research will focus on novel cell culture models to study cancer in systems that closely mimic the in vivo situation, but allow high-throughput approaches.