@article{RossowVeitlVorlovaetal.2018,
  author    = {Rossow, Leonie and Veitl, Simona and Vorlov{\´a}, Sandra and Wax, Jacqueline K. and Kuhn, Anja E. and Maltzahn, Verena and Upcin, Berin and Karl, Franziska and Hoffmann, Helene and G{\"a}tzner, Sabine and Kallius, Matthias and Nandigama, Rajender and Scheld, Daniela and Irmak, Ster and Herterich, Sabine and Zernecke, Alma and Erg{\"u}n, S{\"u}leyman and Henke, Erik},
  title     = {LOX-catalyzed collagen stabilization is a proximal cause for intrinsic resistance to chemotherapy},
  series = {Oncogene},
  volume    = {37},
  journal   = {Oncogene},
  doi       = {10.1038/s41388-018-0320-2},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-227008},
  pages     = {4921-4940},
  year      = {2018},
  abstract  = {The potential of altering the tumor ECM to improve drug response remains fairly unexplored. To identify targets for modification of the ECM aiming to improve drug response and overcome resistance, we analyzed expression data sets from pre-treatment patient cohorts. Cross-evaluation identified a subset of chemoresistant tumors characterized by increased expression of collagens and collagen-stabilizing enzymes. We demonstrate that strong collagen expression and stabilization sets off a vicious circle of self-propagating hypoxia, malignant signaling, and aberrant angiogenesis that can be broken by an appropriate auxiliary intervention: Interfering with collagen stabilization by inhibition of lysyl oxidases significantly enhanced response to chemotherapy in various tumor models, even in metastatic disease. Inhibition of collagen stabilization by itself can reduce or enhance tumor growth depending on the tumor type. The mechanistical basis for this behavior is the dependence of the individual tumor on nutritional supply on one hand and on high tissue stiffness for FAK signaling on the other.},
  language  = {en}
}
@article{SchuetzeRoehringVorlovaetal.2015,
  author    = {Sch{\"u}tze, Friedrich and R{\"o}hring, Florian and Vorlov{\´a}, Sandra and G{\"a}tzner, Sabine and Kuhn, Anja and Erg{\"u}n, S{\"u}leyman and Henke, Erik},
  title     = {Inhibition of lysyl oxidases improves drug diffusion and increases efficacy of cytotoxic treatment in 3D tumor models},
  series = {Scientific Reports},
  volume    = {5},
  journal   = {Scientific Reports},
  number    = {17576},
  doi       = {10.1038/srep17576},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-145109},
  year      = {2015},
  abstract  = {Tumors are characterized by a rigid, highly cross-linked extracellular matrix (ECM), which impedes homogeneous drug distribution and potentially protects malignant cells from exposure to therapeutics. Lysyl oxidases are major contributors to tissue stiffness and the elevated expression of these enzymes observed in most cancers might influence drug distribution and efficacy. We examined the effect of lysyl oxidases on drug distribution and efficacy in 3D in vitro assay systems. In our experiments elevated lysyl oxidase activity was responsible for reduced drug diffusion under hypoxic conditions and consequently impaired cytotoxicity of various chemotherapeutics. This effect was only observed in 3D settings but not in 2D-cell culture, confirming that lysyl oxidases affect drug efficacy by modification of the ECM and do not confer a direct desensitizing effect. Both drug diffusion and efficacy were strongly enhanced by inhibition of lysyl oxidases. The results from the in vitro experiments correlated with tumor drug distribution in vivo, and predicted response to therapeutics in murine tumor models. Our results demonstrate that lysyl oxidase activity modulates the physical barrier function of ECM for small molecule drugs influencing their therapeutic efficacy. Targeting this process has the potential to significantly enhance therapeutic efficacy in the treatment of malignant diseases.},
  language  = {en}
}