Collaborative Research Center 1399

Small cell lung cancer (SCLC) is the most aggressive lung cancer subtype and little progress has been made in understanding the molecular mechanisms causing this devastating disease. No mechanistic explanation exists for a central clinical hallmark: While SCLC typically presents with initial sensitivity against chemotherapy, the disease almost inevitably relapses. Recent discoveries in SCLC genomics and transcriptomics have now provided first mechanistic insight into the biology of this deadly disease.

Here, we propose to leverage on this knowledge and launch an orchestrated pursuit of mechanistic analyses aimed at advancing our understanding of the molecular pathogenesis of SCLC with the goal of transferring our novel discoveries into clinical application. Our consortium is highly interdisciplinary, covering expertise in biochemistry and signaling, structural biology, and structure-guided drug design, cancer immunology, mouse models, cancer genomics, computational genomics, molecular pathology, as well as clinical trials. Members of our consortium have a track record of interdisciplinary, cross-faculty collaboration. We build our consortium on a portfolio of established technological platforms involving genomics, immunomics, cellular models, genetic mouse models and imaging, as well as computational efforts to understand the molecular evolution of SCLC. Particular emphasis is placed on functionally interrogating the discoveries made in high-throughput assays in subsequent mechanistic experiments. Our scientific efforts are intimately linked to the clinic through a translational platform, which facilitates the longitudinal molecular monitoring of patients, thus providing mechanisms of evolution and adaptation to therapy. We anticipate that these efforts will reveal possible entry routes for targeted therapeutic intervention that can overcome drug resistance in this cancer, thus paving the way for curative therapeutic approaches in the future. In addition to our scientific goals, this CRC will strengthen the precision medicine lighthouse in Cologne and help connecting interdisciplinary research across different cancer entities. A significant part of this endeavor therefore is to create measures for training of young scientists. In particular, the proposed integrated training network will foster the structured scientific training of our students and physicians through several classes and courses, quarterly symposia and established exchange programs with the Massachusetts Institute of Technology and Stanford University.