In J04, L. Fröhlich will investigate the regulatory mechanisms that enable SCLC cells to adapt to chemotherapy and transition into drug-tolerant and resistant states. Building on previous work on MYC/MIZ1-dependent transcriptional and epigenetic regulation, the project will integrate time-resolved multi-omic and single-cell profiling with computational genomics, machine learning and AI-based modeling to predict the regulatory programs underlying therapy-induced cell-state plasticity. Experimental perturbation of candidate regulators will define their causal contribution to cell-state transitions and therapy response. By linking predictive computational approaches with mechanistic validation, J04 aims to reveal how resistant states emerge and identify new opportunities to interfere with the development of therapy resistance.