@article{KimpelSchindlerSchmidtPenningtonetal.2023,
  author    = {Kimpel, Otilia and Schindler, Paul and Schmidt-Pennington, Laura and Altieri, Barbara and Megerle, Felix and Haak, Harm and Pittaway, James and Dischinger, Ulrich and Quinkler, Marcus and Mai, Knut and Kroiss, Matthias and Polat, B{\"u}lent and Fassnacht, Martin},
  title     = {Efficacy and safety of radiation therapy in advanced adrenocortical carcinoma},
  series = {British Journal of Cancer},
  volume    = {128},
  journal   = {British Journal of Cancer},
  number    = {4},
  doi       = {10.1038/s41416-022-02082-0},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-324411},
  pages     = {586-593},
  year      = {2023},
  abstract  = {Background International guidelines emphasise the role of radiotherapy (RT) for the management of advanced adrenocortical carcinoma (ACC). However, the evidence for this recommendation is very low. Methods We retrospectively analysed all patients who received RT for advanced ACC in five European centres since 2000. Primary endpoint: time to progression of the treated lesion (tTTP). Secondary endpoints: best objective response, progression-free survival (PFS), overall survival (OS), adverse events, and the establishment of predictive factors by Cox analyses. Results In total, 132 tumoural lesions of 80 patients were treated with conventional RT (cRT) of 50-60 Gy (n = 20) or 20-49 Gy (n = 69), stereotactic body RT of 35-50 Gy (SBRT) (n = 36), or brachytherapy of 12-25 Gy (BT) (n = 7). Best objective lesional response was complete (n = 6), partial (n = 52), stable disease (n = 60), progressive disease (n = 14). Median tTTP was 7.6 months (1.0-148.6). In comparison to cRT\(_{20-49Gy}\), tTTP was significantly longer for cRT\(_{50-60Gy}\) (multivariate adjusted HR 0.10; 95\% CI 0.03-0.33; p < 0.001) and SBRT (HR 0.31; 95\% CI 0.12-0.80; p = 0.016), but not for BT (HR 0.66; 95\% CI 0.22-1.99; p = 0.46). Toxicity was generally mild and moderate with three grade 3 events. No convincing predictive factors could be established. Conclusions This largest published study on RT in advanced ACC provides clear evidence that RT is effective in ACC.},
  language  = {en}
}
@article{KugerCoerekPolatetal.2014,
  author    = {Kuger, Sebastian and C{\"o}rek, Emre and Polat, B{\"u}lent and K{\"a}mmerer, Ulrike and Flentje, Michael and Djuzenova, Cholpon S.},
  title     = {Novel PI3K and mTOR Inhibitor NVP-BEZ235 Radiosensitizes Breast Cancer Cell Lines under Normoxic and Hypoxic Conditions},
  doi       = {10.4137/BCBCR.S13693},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-112708},
  year      = {2014},
  abstract  = {In the present study, we assessed, if the novel dual phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) inhibitor NVP-BEZ235 radiosensitizes triple negative (TN) MDA-MB-231 and estrogen receptor (ER) positive MCF-7 cells to ionizing radiation under various oxygen conditions, simulating different microenvironments as occurring in the majority of breast cancers (BCs). Irradiation (IR) of BC cells cultivated in hypoxic conditions revealed increased radioresistance compared to normoxic controls. Treatment with NVP-BEZ235 completely circumvented this hypoxia-induced effects and radiosensitized normoxic, reoxygenated, and hypoxic cells to similar extents. Furthermore, NVP-BEZ235 treatment suppressed HIF-1α expression and PI3K/mTOR signaling, induced autophagy, and caused protracted DNA damage repair in both cell lines in all tested oxygen conditions. Moreover, after incubation with NVP-BEZ235, MCF-7 cells revealed depletion of phospho-AKT and considerable signs of apoptosis, which were signifi-cantly enhanced by radiation. Our findings clearly demonstrate that NVP-BEZ235 has a clinical relevant potential as a radiosensitizer in BC treatment.},
  language  = {en}
}
@article{FischerHartmannReisslandetal.2022,
  author    = {Fischer, Thomas and Hartmann, Oliver and Reissland, Michaela and Prieto-Garcia, Cristian and Klann, Kevin and Pahor, Nikolett and Sch{\"u}lein-V{\"o}lk, Christina and Baluapuri, Apoorva and Polat, B{\"u}lent and Abazari, Arya and Gerhard-Hartmann, Elena and Kopp, Hans-Georg and Essmann, Frank and Rosenfeldt, Mathias and M{\"u}nch, Christian and Flentje, Michael and Diefenbacher, Markus E.},
  title     = {PTEN mutant non-small cell lung cancer require ATM to suppress pro-apoptotic signalling and evade radiotherapy},
  series = {Cell \& Bioscience},
  volume    = {12},
  journal   = {Cell \& Bioscience},
  issn      = {2045-3701},
  doi       = {10.1186/s13578-022-00778-7},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-299865},
  year      = {2022},
  abstract  = {Background Despite advances in treatment of patients with non-small cell lung cancer, carriers of certain genetic alterations are prone to failure. One such factor frequently mutated, is the tumor suppressor PTEN. These tumors are supposed to be more resistant to radiation, chemo- and immunotherapy. Results We demonstrate that loss of PTEN led to altered expression of transcriptional programs which directly regulate therapy resistance, resulting in establishment of radiation resistance. While PTEN-deficient tumor cells were not dependent on DNA-PK for IR resistance nor activated ATR during IR, they showed a significant dependence for the DNA damage kinase ATM. Pharmacologic inhibition of ATM, via KU-60019 and AZD1390 at non-toxic doses, restored and even synergized with IR in PTEN-deficient human and murine NSCLC cells as well in a multicellular organotypic ex vivo tumor model. Conclusion PTEN tumors are addicted to ATM to detect and repair radiation induced DNA damage. This creates an exploitable bottleneck. At least in cellulo and ex vivo we show that low concentration of ATM inhibitor is able to synergise with IR to treat PTEN-deficient tumors in genetically well-defined IR resistant lung cancer models.},
  language  = {en}
}