Affiliation: Johann Wolfgang Goethe University
- Liese J, Abhari B, Fulda S. Smac mimetic and oleanolic acid synergize to induce cell death in human hepatocellular carcinoma cells. Cancer Lett. 2015;365:47-56 pubmed publisher..In conclusion, cotreatment of Smac mimetic and OA represents a novel approach for the induction of cell death in HCC and implicates further studies. ..
- Hehlgans S, Oppermann J, Reichert S, Fulda S, RÃ¶del C, RÃ¶del F. The SMAC mimetic BV6 sensitizes colorectal cancer cells to ionizing radiation by interfering with DNA repair processes and enhancing apoptosis. Radiat Oncol. 2015;10:198 pubmed publisher..Our results demonstrate IAP targeting as a promising strategy to counteract radiation resistance of colorectal cancer cells. ..
- ..Smac mimetics are currently undergoing clinical evaluation in phase I/II trials, demonstrating that therapeutic targeting of IAP proteins has reached the clinical stage. ..
- Lindemann C, Marschall V, Weigert A, Klingebiel T, Fulda S. Smac Mimetic-Induced Upregulation of CCL2/MCP-1 Triggers Migration and Invasion of Glioblastoma Cells and Influences the Tumor Microenvironment in a Paracrine Manner. Neoplasia. 2015;17:481-9 pubmed publisher..These findings provide novel insights into the biological functions of Smac mimetics with important implications for the development of Smac mimetics as cancer therapeutics. ..
- Fulda S. Safety and tolerability of TRAIL receptor agonists in cancer treatment. Eur J Clin Pharmacol. 2015;71:525-7 pubmed publisher..Currently, the challenge resides in the development of rational TRAIL-based combination therapies with potent TRAIL receptor agonists in order to exploit the potential of death receptor targeting for cancer therapy. ..
- Fulda S. Targeting extrinsic apoptosis in cancer: Challenges and opportunities. Semin Cell Dev Biol. 2015;39:20-5 pubmed publisher..A better understanding of these signaling networks and their deregulation in human cancers is anticipated to open new perspectives for the development of apoptosis-targeted therapies for the treatment of cancer. ..
- Meister M, Boedicker C, Klingebiel T, Fulda S. Hedgehog signaling negatively co-regulates BH3-only protein Noxa and TAp73 in TP53-mutated cells. Cancer Lett. 2018;429:19-28 pubmed publisher..These findings suggest that Gli1 represses Noxa and TAp73, possibly via EGR1. These findings could be exploited for the treatment of Hh-driven tumors, e.g. for their sensitization to chemotherapeutic agents. ..
- Bake V, Roesler S, Eckhardt I, Belz K, Fulda S. Synergistic interaction of Smac mimetic and IFNÎ± to trigger apoptosis in acute myeloid leukemia cells. Cancer Lett. 2014;355:224-31 pubmed publisher..In conclusion, the identification of a novel synergistic antileukemic combination of Smac mimetic and IFNÎ± has important implications for the development of innovative treatment strategies in AML. ..
- Stehle A, Hugle M, Fulda S. Eribulin synergizes with Polo-like kinase 1 inhibitors to induce apoptosis in rhabdomyosarcoma. Cancer Lett. 2015;365:37-46 pubmed publisher..e. Eribulin and BI 2536, has important implications for the development of more effective treatment strategies for RMS. ..
- Enßle J, Boedicker C, Wanior M, Vogler M, Knapp S, Fulda S. Co-targeting of BET proteins and HDACs as a novel approach to trigger apoptosis in rhabdomyosarcoma cells. Cancer Lett. 2018;428:160-172 pubmed publisher..These findings indicate that combinatorial use of BET and HDACIs may represent a promising new strategy for the treatment of RMS. ..
- Hugle M, Fulda S. Dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor NVP-BEZ235 synergizes with chloroquine to induce apoptosis in embryonal rhabdomyosarcoma. Cancer Lett. 2015;360:1-9 pubmed publisher..This identification of a synthetic lethality of BEZ235 and CQ has important implications for the development of molecular targeted therapies for RMS. ..
- ..Some of these concepts have already been transferred into clinical application in oncology and may open new perspectives for the treatment of cancer. ..
- Lange M, Abhari B, Hinrichs T, Fulda S, Liese J. Identification of a novel oxidative stress induced cell death by Sorafenib and oleanolic acid in human hepatocellular carcinoma cells. Biochem Pharmacol. 2016;118:9-17 pubmed publisher..In conclusion, OA represents a novel approach to increase the sensitivity of HCC cells to Sorafenib via oxidative stress. ..
- Meister M, Boedicker C, Graab U, Hugle M, Hahn H, Klingebiel T, et al. Arsenic trioxide induces Noxa-dependent apoptosis in rhabdomyosarcoma cells and synergizes with antimicrotubule drugs. Cancer Lett. 2016;381:287-95 pubmed publisher..In summary, ATO exerts antitumor activity against RMS, especially in combination with antimicrotubule drugs. These findings have important implications for the development of novel therapeutic strategies for RMS. ..
- Gerges S, Rohde K, Fulda S. Cotreatment with Smac mimetics and demethylating agents induces both apoptotic and necroptotic cell death pathways in acute lymphoblastic leukemia cells. Cancer Lett. 2016;375:127-132 pubmed publisher..This opens new perspectives to overcome apoptosis resistance with important implications for the development of new treatment strategies for ALL. ..
- Reiter M, Eckhardt I, Haferkamp A, Fulda S. Smac mimetic sensitizes renal cell carcinoma cells to interferon-Î±-induced apoptosis. Cancer Lett. 2016;375:1-8 pubmed publisher..In conclusion, the combination approach of IFNÎ± and BV6 represents a promising strategy for cooperative induction of apoptosis in RCC cells, which warrants further investigation. ..
- HaÃŸ C, Belz K, Schoeneberger H, Fulda S. Sensitization of acute lymphoblastic leukemia cells for LCL161-induced cell death by targeting redox homeostasis. Biochem Pharmacol. 2016;105:14-22 pubmed publisher..These results emphasize that inhibition of antioxidant defense mechanisms can serve as a potent approach to prime ALL cells for LCL161-induced cell death. ..
- Fulda S. Promises and Challenges of Smac Mimetics as Cancer Therapeutics. Clin Cancer Res. 2015;21:5030-6 pubmed publisher..e., GDC-0917/CUDC-427, LCL161, AT-406/Debio1143, HGS1029, and TL32711/birinapant). This review discusses the promise as well as some challenges at the translational interface of exploiting Smac mimetics as cancer therapeutics. ..
- Dolgikh N, Hugle M, Vogler M, Fulda S. NRAS-Mutated Rhabdomyosarcoma Cells Are Vulnerable to Mitochondrial Apoptosis Induced by Coinhibition of MEK and PI3Kα. Cancer Res. 2018;78:2000-2013 pubmed publisher..i>Cancer Res; 78(8); 2000-13. ©2018 AACR. ..
- Schmidt N, Haydn T, Schneider I, Busch H, Boerries M, Fulda S. Smac mimetic induces an early wave of gene expression via NF-κB and AP-1 and a second wave via TNFR1 signaling. Cancer Lett. 2018;421:170-185 pubmed publisher..Thus, BV6 alters gene expression in a time- as well as TNFR1-dependent manner. ..
- Hussain M, Zimmermann V, van Wijk S, Fulda S. Mouse lung fibroblasts are highly susceptible to necroptosis in a reactive oxygen species-dependent manner. Biochem Pharmacol. 2018;153:242-247 pubmed publisher..Thus, our study demonstrates for the first time that MLFs are prone to undergo necroptosis in response to a prototypic necroptotic stimulus and identifies ROS as important mediators of TSZ-triggered necroptosis. ..
- Hannes S, Abhari B, Fulda S. Smac mimetic triggers necroptosis in pancreatic carcinoma cells when caspase activation is blocked. Cancer Lett. 2016;380:31-8 pubmed publisher..By demonstrating that Smac mimetics can bypass resistance to apoptosis by triggering necroptosis as an alternative form of programmed cell death, our findings have important implications for the design of new treatment concepts for PC. ..
- Cekay M, Roesler S, Frank T, Knuth A, Eckhardt I, Fulda S. Smac mimetics and type II interferon synergistically induce necroptosis in various cancer cell lines. Cancer Lett. 2017;410:228-237 pubmed publisher..This is the first report showing that Smac mimetics synergize with IFNÎ³ to trigger necroptosis in apoptosis-resistant cancer cells with important implications for Smac mimetic-based strategies for the treatment of cancer. ..
- Fulda S. Smac Mimetics to Therapeutically Target IAP Proteins in Cancer. Int Rev Cell Mol Biol. 2017;330:157-169 pubmed publisher..At present, several Smac mimetics are being evaluated in early clinical trials. The current review provides an overview on the potential of Smac mimetics as cancer therapeutics to target IAP proteins for cancer therapy. ..
- Fulda S, Vucic D. Targeting IAP proteins for therapeutic intervention in cancer. Nat Rev Drug Discov. 2012;11:109-24 pubmed publisher..This Review provides an update on IAP protein biology as well as current and future perspectives on targeting IAP proteins for therapeutic intervention in human malignancies. ..
- Fulda S. Therapeutic opportunities based on caspase modulation. Semin Cell Dev Biol. 2018;82:150-157 pubmed publisher..Thus, targeted modulation of caspase activation and apoptosis represents a promising approach for the development of new therapeutic options to elucidate cancer cell death. ..
- Faqar Uz Zaman S, Heinicke U, Meister M, Vogler M, Fulda S. BCL-xL-selective BH3 mimetic sensitizes rhabdomyosarcoma cells to chemotherapeutics by activation of the mitochondrial pathway of apoptosis. Cancer Lett. 2018;412:131-142 pubmed publisher..In conclusion, our findings provide a rationale for the combination of BH3 mimetics with conventional chemotherapeutic agents to increase the chemosensitivity of RMS. ..
- Bhatti I, Abhari B, Fulda S. Identification of a synergistic combination of Smac mimetic and Bortezomib to trigger cell death in B-cell non-Hodgkin lymphoma cells. Cancer Lett. 2017;405:63-72 pubmed publisher..The discovery of this synergistic combination that is effective even when apoptosis is blocked has important implications for the development of new treatment strategies for B-cell NHL. ..
- Probst L, Dächert J, Schenk B, Fulda S. Lipoxygenase inhibitors protect acute lymphoblastic leukemia cells from ferroptotic cell death. Biochem Pharmacol. 2017;140:41-52 pubmed publisher..By providing new insights into the molecular regulation of ferroptosis, our study contributes to the development of novel treatment strategies to reactivate programmed cell death in ALL. ..
- Fulda S. Exploiting inhibitor of apoptosis proteins as therapeutic targets in hematological malignancies. Leukemia. 2012;26:1155-65 pubmed publisher..As some of these strategies have already entered the stage of clinical evaluation, for example, in leukemia, an update on this promising molecular-targeted strategy to interfere with apoptotic pathways is of broad interest. ..
- Fulda S. Molecular pathways: targeting death receptors and smac mimetics. Clin Cancer Res. 2014;20:3915-20 pubmed publisher..Such combinations might therefore be of special interest for being included in the ongoing evaluation of Smac mimetics in early clinical trials. ..
- Chromik J, Safferthal C, Serve H, Fulda S. Smac mimetic primes apoptosis-resistant acute myeloid leukaemia cells for cytarabine-induced cell death by triggering necroptosis. Cancer Lett. 2014;344:101-109 pubmed publisher..These findings have important implications for Smac mimetic-based strategies to bypass apoptosis resistance of AML. ..