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
Abstract
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. Personalized treatment for cancer patients relies on the deep characterization of tumor cells from patient biopsies. In this study, functional multi-omics profiling of a pan-cancer cohort of malignant serous effusions (MSE) finds strong coherence between MSE and matched solid tumors, underlining the feasibility and utility of multi-modal MSE-based precision oncology.