Mechanisms of drug sensitivity and resistance in SCLC (B01)

• Subject Area: Cell Biology ; General Genetics and Functional Genome Biology ; Hematology, Oncology
• Term: since 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 413326622

R. Thomas and J. George will extend their work in the area of evolutionary processes driving acquired resistance. They will put particular emphasis on studying mechanisms underlying resistance to first-line platinum-based chemotherapy. In their preliminary studies, they found that both, tumors at relapse exhibited an expansion of earlier derivatives of the common ancestral clone. The team will now study several additional cases of response and resistance to immunotherapy with the goal of understanding the differences compared to evolution under chemotherapy. In an orthogonal approach, they will pursue functional experiments with the aim of mechanistically characterizing the role of the various alterations they identified in the common ancestor. They will employ methods of genetic manipulation in vitro and in vivo in patient-derived model systems and GEMMs, ultimately with the goal of identifying potentially therapeutically relevant vulnerabilities of the most relevant cellular component of SCLC.

• DFG Programme: Collaborative Research Centres
• Subproject of: SFB 1399: Mechanisms of drug sensitivity and resistance in small cell lung cancer
• Applicant Institution: Universität zu Köln
• Project Heads: Professorin Dr. Julie George, since 7/2023; Professor Dr. Roman Thomas