@article{RauertWunderlichBerberichRosenwaldetal.2018,
  author    = {Rauert-Wunderlich, Hilka and Berberich, Ingolf and Rosenwald, Andreas and Rudelius, Martina},
  title     = {CD40L mediated alternative NF kappa B-signaling induces resistance to BCR-inhibitors in patients with mantle cell lymphoma},
  series = {Cell Death \& Disease},
  journal   = {Cell Death \& Disease},
  number    = {9},
  doi       = {10.1038/s41419-017-0157-6},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-225027},
  pages     = {86, 1-9},
  year      = {2018},
  abstract  = {Drug resistance is a significant obstacle in cancer treatment and therefore a frequent subject of research. Developed or primary resistance limits the treatment success of inhibitors of the B cell receptor (BCR) pathway in mantle cell lymphoma (MCL) patients. Recent research has highlighted the role of the nuclear factor-kappa B (NF kappa B) pathway in the context of resistance to BCR inhibitors in MCL. In this study, we analyzed the dependency of MCL cell lines on NF kappa B signaling and illustrated the ability of CD40L to activate the alternative NF kappa B pathway in MCL. This activation leads to independency of classical NF kappa B signaling and results in resistance to BCR inhibitors. Therefore, ligands (such as CD40L) and their activation of the alternative NF kappa B pathway have a major impact on the drug response in MCL. Furthermore, this study indicates a protective role for cells expressing specific ligands as microenvironmental niches for MCL cells and underlines the significance of therapeutically targeting alternative NF kappa B signaling in MCL.},
  language  = {en}
}
@article{RudeliusRosenfeldtLeichetal.2019,
  author    = {Rudelius, Martina and Rosenfeldt, Mathias Tillmann and Leich, Ellen and Rauert-Wunderlich, Hilka and Solimando, Antonio Giovanni and Ott, German and Rosenwald, Andreas and Beilhack, Andreas},
  title     = {Inhibition of focal adhesion kinase overcomes resistance of mantle cell lymphoma to ibrutinib in the bone marrow microenvironment},
  series = {Haematologica},
  volume    = {103},
  journal   = {Haematologica},
  number    = {1},
  doi       = {10.3324/haematol.2017.177162},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-227117},
  pages     = {116-125},
  year      = {2019},
  abstract  = {Mantle cell lymphoma and other lymphoma subtypes often spread to the bone marrow, and stromal interactions mediated by focal adhesion kinase frequently enhance survival and drug resistance of the lymphoma cells. To study the role of focal adhesion kinase in mantle cell lymphoma, immunohistochemistry of primary cases and functional analysis of mantle cell lymphoma cell lines and primary mantle cell lymphoma cells co-cultured with bone marrow stromal cells (BMSC) using small molecule inhibitors and RNAi-based focal adhesion kinase silencing was performed. We showed that focal adhesion kinase is highly expressed in bone marrow infiltrates of mantle cell lymphoma and in mantle cell lymphoma cell lines. Stroma-mediated activation of focal adhesion kinase led to activation of multiple kinases (AKT, p42/44 and NF-kappa B), that are important for prosurvival and proliferation signaling. Interestingly, RNAi-based focal adhesion kinase silencing or inhibition with small molecule inhibitors (FAKi) resulted in blockage of targeted cell invasion and induced apoptosis by inactivation of multiple signaling cascades, including the classic and alternative NF-kappa B pathway. In addition, the combined treatment of ibrutinib and FAKi was highly synergistic, and ibrutinib resistance of mantle cell lymphoma could be overcome. These data demonstrate that focal adhesion kinase is important for stroma-mediated survival and drug resistance in mantle cell lymphoma, providing indications for a targeted therapeutic strategy.},
  subject      = {Multiple},
  language  = {en}
}