Decoding epigenetic subtypes, resistance mechanisms and vulnerabilities of small cell lung cancer (B05)

• Subject Area: General Genetics and Functional Genome Biology ; Hematology, Oncology
• Term: since 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 413326622

R. Hänsel-Hertsch and his team will employ their newly developed technologies to characterize the epigenetic mechanisms driving transcription factor activation and subtype plasticity in acquired drug resistance in SCLC. In the first funding period, they found increased chromatin accessibility and occupancy of MYC, YAP1, H2A.Z, and decreased G-quadruplex secondary structure formation in chemo-resistant SCLC, which they will now seek to validate and corroborate by studying additional specimens from mice and patients at relapse using single-cell omics profiling. They will then test the hypothesis that these epigenetic alterations cause actionable vulnerabilities by genetic manipulation of newly identified transcription factor involvement. The team will further test, whether particular proteins associated with these epigenetic alterations are also amenable to therapeutic intervention using small molecules.

• 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 Head: Robert Hänsel-Hertsch, Ph.D.