KINETO Lab’s project manager and biologist researcher Dr. Sára Surguta will present the poster with the title „Proteomic insights into metastatic small cell lung cancer using patient derived xenograft models”, where findings demonstrate that the proteomic identity of SCLC tumors is largely preserved during serial passaging in PDTX models, while site-specific adaptations emerge in distinct metastatic microenvironments. (Poster number: 2108; Abstract Number: 3777; Time of Presentation: 20^th of April 2026 from 9:00AM to 12:00PM; Name of Session: Characterization of Metastases by Imaging and Profiling).

Small cell lung cancer (SCLC) is one of the most aggressive solid malignancies with limited treatment options. Access to clinically relevant SCLC tissue is restricted because surgical resection is rare in metastatic disease, making this cancer type difficult to study. Through our multicenter rapid research autopsy (RRA) program, however, we are able to collect not only primary tumors but also multiple metastatic lesions. In this program, rapid autopsies are performed within four hours after death to preserve tissue integrity and ensure suitability for downstream analyses. In the current project, we analyzed samples from seven patients with histologically confirmed SCLC, including primary and metastatic lesions, as well as their corresponding patient-derived tumor xenografts (PDTXs) serially passaged through three generations. To assess whether the original tissue architecture and intratumoral heterogeneity are preserved across PDTX generations, we performed immunohistochemical and proteomic analyses, comparing molecular profiles between the original tumors and their corresponding PDTX models. SCLC primary and metastatic specimens, including matched PDTX–tumor pairs, confirmed that the histologic architecture of the tumors of origin was preserved in the corresponding PDTX models. Proteomic profiling revealed that samples clustered primarily by patient and anatomical site, reflecting strong lineage fidelity across PDTX generations. The mean within-lineage correlation was high (typically >0.8), and correlation heatmaps showed tight clustering across PDTX generations from the same lineage. Across all patients, the only pathways consistently and significantly downregulated in PDTX models compared with the original tumors were the ECM–receptor interaction and Complement and Coagulation Cascade pathways. When analyzing metastatic PDTX samples, we compared liver and lymph node metastases with their corresponding primary patient tumors across PDTX generations. Among the top pathways consistently enriched across all generations, lymph node metastases showed upregulation of proteins involved in ECM–receptor interaction and EMT pathways. In contrast, when compared with their corresponding primary tumors, liver metastases exhibited upregulation of fatty acid metabolism and peroxisome proliferator–activated receptor (PPAR) signaling pathways, and showed concurrent downregulation of EMT, ECM–receptor interaction, E2F targets, and G2M checkpoint pathways. These findings demonstrate that the proteomic identity of SCLC tumors is largely preserved during serial passaging in PDTX models, while site-specific adaptations emerge in distinct metastatic microenvironments.