Identification and characterization of molecular vulnerabilities in SCLC (A01)

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

C. Reinhardt and F. Beleggia will employ genetically engineered mouse models and in vivo screening tools, to address fundamental questions in SCLC biology and treatment response. The team will conduct in-depth studies employing different GEMMs coupled with high-resolution single-cell analyses aimed at identifying the key steps in malignant transformation of pulmonary neuroendocrine cells (PNECs). A particular emphasis will be based on studying the impact of tobacco smoke in the context of engineered alterations of Tp53 and Rb1. They will also seek to identify, which molecular features govern response to inhibitors of the DNA damage response and of the cell cycle that are being explored clinically. Finally, building on their observations made during the first funding period, they will seek to characterize the molecular mechanism of action of inhibitors of glutamatergic signaling in vivo, ultimately, with the goal of identifying potent and selective entry routes for therapeutic intervention.

• 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: Dr. Filippo Beleggia, since 7/2023; Professor Dr. Christian Reinhardt, since 7/2019; Professor Dr. Frank Thomas Wunderlich, from 7/2019 until 6/2023