GRK 3110:  Tumor Heterogeneity and Genomic Instability in Lung Cancer – From Basic Mechanisms to Clinical Implications

• Subject Area: Medicine
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 537841948

Non-small cell lung cancer represents the leading cause of death from cancer world-wide. The last decade witnessed major areas of innovation in treatment. Recent independent evaluation of the national Network Genomic Medicine steered by two PIs of this IRTG (JW and RB) revealed that comprehensive evaluation of treatment options led to significant survival benefits. However, still huge medical needs remain for those tumors that escape from targeted and immune therapies early on and more so for those that elicit no further genomically defined driver or resistance mutation. Therefore, this IRTG aims to address mechanisms of resistance within four defined areas: (1) genomic instability driven by p53 deficiency, (2) instability in tumor genomes and effects on microenvironment driven by metabolic shift and stress, (3) heterogeneity in KRAS-driven tumors and tumors with germline variants for lung cancer risk and (4) in silico technologies that reconstruct evolutionary trajectories and AI-based analysis of tumor features. Based on these, we expect to generate informative models predicting risk and mechanisms of resistance and (poly)clonal evolution in locally advanced or systemic lung cancers and therapy. Our aim is to identify key parameters of resistance evolution in a clinically relevant manner, enabling us to develop and evaluate combined therapies for high-risk genomes using preclinical models. This aligns with the overarching educational goal of the new IRTG program, which is to train the future global generation of researchers and doctors in the rapidly advancing field of translational pathology and oncology. In line with this, one of our key training objectives is to ensure that PhD/MD students complete their research within a four-year timeframe. Additionally, they are encouraged to publish as first authors while receiving a top-tier joint scientific education from two of the world's leading countries in medical research. This bestows them a unique opportunity to be co-supervised by PIs from each country, whilst having the experience of conducting cutting-edge interdisciplinary research in both countries. Such early exposure to an international setting will allow the students to have a head-start in their career development, giving primary international visibility, which will hold as an attractive environment. Our IRTG will integrate the specialized expertise of the CMMC and Molecular Pathology in Cologne with the focused knowledge of data- and IT-driven sciences from SAIHST in Seoul. We will also use the significant differences in Asian and European cancer genomes for a holistic view on genomically informed oncology. While it is crucial for our students to become experts in the research area they choose, we will also implement broader education to encourage interdisciplinary thinking. It will provide a range of various medically-oriented and research-revolving activities to help the students to develop their own career options.

• DFG Programme: International Research Training Groups
• International Connection: South Korea
• Applicant Institution: Universität zu Köln
• IRTG-Partner Institution: Sungkyunkwan University
• Spokesperson: Professor Dr. Reinhard Büttner
• Participating Researchers: Professorin Dr. Katarzyna Bozek; Professorin Dr. Julie George; Professor Dr. Axel Hillmer; Professorin Dr. Silvia von Karstedt; Professorin Dr. Sabine Merkelbach-Bruse; Ka-Won Noh, Ph.D.; Professor Dr. Martin Peifer; Privatdozent Dr. Matthias Scheffler; Professor Dr. Roland Tillmann Ullrich; Professor Dr. Jürgen Wolf
• IRTG-Partner: Spokesperson: Professorin Yoon-La Choi, Ph.D.