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@ARTICLE{Grtz:304587,
      author       = {C. Grätz and P. Changoer and D. M. Chiang and J. Kersting
                      and M. Jaeger and R. Netea-Maier and S. I. Wudy and C.
                      Ludwig and M. List and B. Kirchner$^*$ and M. Reithmair and
                      M. W. Pfaffl},
      title        = {{E}xtracellular vesicle-associated transcriptomic and
                      proteomic biomarkers show in vitro potential for vandetanib
                      treatment monitoring in anaplastic thyroid cancer.},
      journal      = {Scientific reports},
      volume       = {15},
      number       = {1},
      issn         = {2045-2322},
      address      = {[London]},
      publisher    = {Springer Nature},
      reportid     = {DKFZ-2025-01910},
      pages        = {32464},
      year         = {2025},
      abstract     = {Anaplastic thyroid cancer (ATC) is an aggressive and rare
                      disease. Rapid metastasis and limited treatments call for
                      additional therapeutic options, including drug repurposing.
                      The early spreading of ATC highlights the importance of
                      rapid therapy success assessment, which could be achieved by
                      measurement of extracellular vesicle (EV)-associated
                      cell-free RNA in liquid biopsy samples. Recent studies have
                      discovered the potential of the receptor tyrosine kinase
                      inhibitor vandetanib for ATC treatment in vitro and in vivo.
                      Given the rarity of ATC patients receiving off-label
                      vandetanib treatment, acquiring patient samples for clinical
                      studies is a prolonged process, and pre-clinical
                      investigations are needed to elucidate the effects of
                      vandetanib on ATC cells. Here, we present an in vitro study
                      addressing holistic transcriptional and proteomic changes
                      induced in the ATC cell line Cal62 by three doses of
                      vandetanib and quantified by high-throughput methods. By
                      comparing the transcriptional and proteomic data sets and
                      applying dimensional reduction models such as sparse partial
                      least-squares discriminant analysis, we refined a set of 21
                      biomarker candidates. Out of these, we report a final
                      signature of eight transcriptional biomarkers, validated in
                      cellular and cell-free RNA by RT-qPCR and verified for
                      biological significance and discriminatory power by pathway
                      over-representation analysis and partial least-squares
                      regression. This transcriptional biomarker signature can
                      distinguish vandetanib treatment from control in cell-free
                      RNA isolated from Cal62 EVs and can be measured reliably,
                      easily, and quickly using RT-qPCR. Our findings may serve as
                      a basis for future clinical trials with liquid biopsy
                      samples from ATC patients undergoing off-label vandetanib
                      treatment.},
      keywords     = {Anaplastic thyroid cancer (Other) / Biomarker (Other) /
                      Drug repurposing (Other) / Extracellular vesicles (Other) /
                      Liquid biopsy (Other) / Transcriptomics (Other)},
      cin          = {B062},
      ddc          = {600},
      cid          = {I:(DE-He78)B062-20160331},
      pnm          = {312 - Funktionelle und strukturelle Genomforschung
                      (POF4-312)},
      pid          = {G:(DE-HGF)POF4-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40940449},
      pmc          = {pmc:PMC12432113},
      doi          = {10.1038/s41598-025-18319-w},
      url          = {https://inrepo02.dkfz.de/record/304587},
}