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Molecular and functional landscape of malignant serous effusions for precision oncology

  • Rebekka Wegmann,
  • Lorenz Bankel,
  • Yasmin Festl,
  • Kate Lau,
  • Sohyon Lee,
  • Fabian Arnold,
  • Valentina Cappelletti,
  • Aaron Fehr,
  • Paola Picotti,
  • Konstantin J. Dedes,
  • Daniel Franzen,
  • Daniela Lenggenhager,
  • Peter K. Bode,
  • Martin Zoche,
  • Holger Moch,
  • Christian Britschgi,
  • Berend Snijder

摘要

Personalized treatment for patients with advanced solid tumors critically depends on the deep characterization of tumor cells from patient biopsies. Here, we comprehensively characterize a pan-cancer cohort of 150 malignant serous effusion (MSE) samples at the cellular, molecular, and functional level. We find that MSE-derived cancer cells retain the genomic and transcriptomic profiles of their corresponding primary tumors, validating their use as a patient-relevant model system for solid tumor biology. Integrative analyses reveal that baseline gene expression patterns relate to global ex vivo drug sensitivity, while high-throughput drug-induced transcriptional changes in MSE samples are indicative of drug mode of action and acquired treatment resistance. A case study exemplifies the added value of multi-modal MSE profiling for patients who lack genetically stratified treatment options. In summary, our study provides a functional multi-omics view on a pan-cancer solid tumor cohort and underlines the feasibility and utility of MSE-based precision oncology.