GRK 2762:  Heterogeneity, plasticity & dynamics in cancer cell, tumor and normal tissue responses to cancer radiotherapy

• Subject Area: Medicine
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 450917483

Radiotherapy is a central part of the treatment for many cancer types. Locally advanced carcinomas are treated with multimodal combinations with surgery, chemotherapy, and/or molecularly tailored drugs. Recent discoveries have stimulated new clinical trials evaluating the benefits of targeting the DNA damage response, DNA repair, or tumor immune escape with the goal of enhancing the efficacy of radiotherapy. Yet only a fraction of patients responds to such tailored treatments; others do initially not respond, or develop resistance, metastasis, or adverse effects. The inter-patient and inter-tumor heterogeneity in efficacy and toxicity of therapies involving radiotherapy offers largely unexploited avenues for a successful individualization of radiotherapy. So far, radiobiological research aimed at the integration of precision oncology strategies into clinical radiotherapy is still underrepresented. To fill this gap, the proposed RTG will create a multidisciplinary team of highly qualified basic and clinical scientists to explore how the heterogeneity, plasticity, and dynamics of the radiation responses of cancer cells, stromal, and immune cells in tumor and normal tissues affect therapy outcomes. The scientific goal is to discover biological principles underlying individual differences in radiosensitivity, adaptive resistance, and toxicity by translating results from studies using preclinical models and patient samples into interpretable computational models. Thereby we will discover actionable vulnerabilities and valid stratification markers suited to discriminating responders from non-responders and detecting patients at high risk of failure or adverse effects. The educational goal is to train basic and clinical scientists to be capable of addressing research questions related to radiation sciences in oncology in interdisciplinary research teams, and to gain an understanding of biostatistics and data-driven or mechanistic computational modeling. This comprehensive education will allow these scientists to advance the integration of biological insights from radiation sciences and precision cancer medicine into clinical concepts of radiation oncology. These scientists are needed to ensure long-term progress in this important core research area. To achieve this goal, the RTG will provide joint training of excellent young basic and clinical scientists with expert theoretical and practical knowledge in radiation biology and oncology, precision medicine, and computational biology; excellent professional and soft skills; and a broad international network. To optimally integrate both professional groups, the RTG will offer structured 1-year modules for MD students and a regular 4-year modular PhD program for young scientists from natural sciences. Moreover, we will offer rotation positions for young clinical scientists.

• DFG Programme: Research Training Groups
• Applicant Institution: Universität Duisburg-Essen
• Spokesperson: Professorin Dr. Verena Jendrossek
• Participating Researchers: Farnoush Farahpour, Ph.D.; Professorin Dr. Barbara Grüner; Privatdozentin Dr. Nika Guberina; Professor Dr. Daniel Hoffmann; Professorin Katharina Lückerath, Ph.D.; Dr. Johann Matschke; Professor Dr. Tienush Rassaf; Professor Dr. Alexander Schramm; Professor Dr. Jens T. Siveke; Professor Dr. Martin Stuschke; Professorin Dr. Beate Timmermann; Professorin Dr. Astrid M. Westendorf