Klaus Strebhardt

Summary

Affiliation: Frankfurt am Main
Country: Germany

Publications

  1. doi request reprint Paul Ehrlich's magic bullet concept: 100 years of progress
    Klaus Strebhardt
    Klaus Strebhardt is at the Department of Obstetrics and Gynaecology, School of Medicine, J W Goethe University, Theodour Stern Kai 7, 60590 Frankfurt, Germany
    Nat Rev Cancer 8:473-80. 2008
  2. ncbi request reprint The biological relevance of FHL2 in tumour cells and its role as a putative cancer target
    Kai Kleiber
    Department of Gynecology and Obstetrics, Medical School, J W Goethe University, Theodor Stern Kai 7, D 60590 Frankfurt, Germany
    Anticancer Res 27:55-61. 2007
  3. ncbi request reprint Targeting polo-like kinase 1 for cancer therapy
    Klaus Strebhardt
    Department of Obstetrics and Gynecology, School of Medicine, J W Goethe University, Theodore Stern Kai 7, 60590 Frankfurt, Germany
    Nat Rev Cancer 6:321-30. 2006
  4. ncbi request reprint Small molecules keep mitotic kinases in check
    Klaus Strebhardt
    Department of Obstetrics and Gynecology, School of Medicine, J W Goethe University, Theodor Stern Kai 7, 60590 Frankfurt, Germany
    ACS Chem Biol 1:683-6. 2006
  5. doi request reprint Multifaceted polo-like kinases: drug targets and antitargets for cancer therapy
    Klaus Strebhardt
    Department of Obstetrics and Gynaecology, School of Medicine, J W Goethe University, Theodor Stern Kai 7, 60590 Frankfurt, Germany
    Nat Rev Drug Discov 9:643-60. 2010
  6. ncbi request reprint Down-regulation of Polo-like kinase 1 elevates drug sensitivity of breast cancer cells in vitro and in vivo
    Birgit Spänkuch
    Department of Obstetrics and Gynecology, Medical School, J W Goethe University, Frankfurt, Germany
    Cancer Res 66:5836-46. 2006
  7. ncbi request reprint Iressa (ZD 1839) inhibits phosphorylation of three different downstream signal transducers in head and neck cancer (SCCHN)
    Markus Hambek
    Department of Otorhinolaryngology, School of Medicine, J W Goethe University, 60590 Frankfurt, Germany
    Anticancer Res 25:1871-5. 2005
  8. ncbi request reprint Effect of RNA silencing of polo-like kinase-1 (PLK1) on apoptosis and spindle formation in human cancer cells
    Birgit Spänkuch-Schmitt
    Department of Obstetrics and Gynecology, School of Medicine, J W Goethe University, Frankfurt, Germany
    J Natl Cancer Inst 94:1863-77. 2002
  9. ncbi request reprint Long-term downregulation of Polo-like kinase 1 increases the cyclin-dependent kinase inhibitor p21(WAF1/CIP1)
    Nina Naomi Kreis
    Department of Gynecology and Obstetrics, School of Medicine, JW Goethe University, Frankfurt, Germany
    Cell Cycle 8:460-72. 2009
  10. ncbi request reprint Cancer inhibition in nude mice after systemic application of U6 promoter-driven short hairpin RNAs against PLK1
    Birgit Spänkuch
    Department of Obstetrics and Gynecology, School of Medicine, J W Goethe University, Theodor Stern Kai 7, D 60590 Frankfurt, Germany
    J Natl Cancer Inst 96:862-72. 2004

Collaborators

Detail Information

Publications45

  1. doi request reprint Paul Ehrlich's magic bullet concept: 100 years of progress
    Klaus Strebhardt
    Klaus Strebhardt is at the Department of Obstetrics and Gynaecology, School of Medicine, J W Goethe University, Theodour Stern Kai 7, 60590 Frankfurt, Germany
    Nat Rev Cancer 8:473-80. 2008
    ..His postulate of creating 'magic bullets' for use in the fight against human diseases inspired generations of scientists to devise powerful molecular cancer therapeutics...
  2. ncbi request reprint The biological relevance of FHL2 in tumour cells and its role as a putative cancer target
    Kai Kleiber
    Department of Gynecology and Obstetrics, Medical School, J W Goethe University, Theodor Stern Kai 7, D 60590 Frankfurt, Germany
    Anticancer Res 27:55-61. 2007
    ..Since transcription factors control all fundamental developmental and homeostatic processes, transcriptional cofactors like FHL2 are likely to contribute to human carcinogenesis and are of clinical importance in various forms of cancer...
  3. ncbi request reprint Targeting polo-like kinase 1 for cancer therapy
    Klaus Strebhardt
    Department of Obstetrics and Gynecology, School of Medicine, J W Goethe University, Theodore Stern Kai 7, 60590 Frankfurt, Germany
    Nat Rev Cancer 6:321-30. 2006
    ..We address the structural features of the kinase domain and the unique polo-box domain of PLK1 that are most suited for drug development and discuss our current understanding of the therapeutic potential of PLK1...
  4. ncbi request reprint Small molecules keep mitotic kinases in check
    Klaus Strebhardt
    Department of Obstetrics and Gynecology, School of Medicine, J W Goethe University, Theodor Stern Kai 7, 60590 Frankfurt, Germany
    ACS Chem Biol 1:683-6. 2006
    ..Compounds targeting the nucleotide binding pockets of polo-like kinases in particular provide significant new insights into the molecular mechanisms controlling cell-division phenotypes...
  5. doi request reprint Multifaceted polo-like kinases: drug targets and antitargets for cancer therapy
    Klaus Strebhardt
    Department of Obstetrics and Gynaecology, School of Medicine, J W Goethe University, Theodor Stern Kai 7, 60590 Frankfurt, Germany
    Nat Rev Drug Discov 9:643-60. 2010
    ..In this article, recent insights into the biology of PLKs will be reviewed, with an emphasis on their role in malignant transformation, and progress in the development of small-molecule PLK1 inhibitors will be examined...
  6. ncbi request reprint Down-regulation of Polo-like kinase 1 elevates drug sensitivity of breast cancer cells in vitro and in vivo
    Birgit Spänkuch
    Department of Obstetrics and Gynecology, Medical School, J W Goethe University, Frankfurt, Germany
    Cancer Res 66:5836-46. 2006
    ....
  7. ncbi request reprint Iressa (ZD 1839) inhibits phosphorylation of three different downstream signal transducers in head and neck cancer (SCCHN)
    Markus Hambek
    Department of Otorhinolaryngology, School of Medicine, J W Goethe University, 60590 Frankfurt, Germany
    Anticancer Res 25:1871-5. 2005
    ..We conclude that Iressa has a high potency to inhibit nuclear gene transcription responsible for cell cycle progression. Furthermore, dose reduction of Iressa in the case of toxicity may not severely influence the response to treatment...
  8. ncbi request reprint Effect of RNA silencing of polo-like kinase-1 (PLK1) on apoptosis and spindle formation in human cancer cells
    Birgit Spänkuch-Schmitt
    Department of Obstetrics and Gynecology, School of Medicine, J W Goethe University, Frankfurt, Germany
    J Natl Cancer Inst 94:1863-77. 2002
    ..To investigate the role of PLK1 in neoplastic proliferation, we used the technique of RNA interference...
  9. ncbi request reprint Long-term downregulation of Polo-like kinase 1 increases the cyclin-dependent kinase inhibitor p21(WAF1/CIP1)
    Nina Naomi Kreis
    Department of Gynecology and Obstetrics, School of Medicine, JW Goethe University, Frankfurt, Germany
    Cell Cycle 8:460-72. 2009
    ..Importantly, HeLa cells with reduced level of Plk1, which induces an increase of p21, p73 and Bax, are more sensitive to some chemotherapeutic agents, such as cisplatin...
  10. ncbi request reprint Cancer inhibition in nude mice after systemic application of U6 promoter-driven short hairpin RNAs against PLK1
    Birgit Spänkuch
    Department of Obstetrics and Gynecology, School of Medicine, J W Goethe University, Theodor Stern Kai 7, D 60590 Frankfurt, Germany
    J Natl Cancer Inst 96:862-72. 2004
    ..We used a xenograft mouse model to determine whether an RNA interference-based strategy that used short hairpin RNAs (shRNAs) to suppress PLK1 expression could inhibit tumor growth in vivo...
  11. pmc Targeting cyclin B1 inhibits proliferation and sensitizes breast cancer cells to taxol
    Ilija Androic
    Department of Obstetrics and Gynecology, School of Medicine, J, W, Goethe University, Theodor Stern Kai 7, 60590 Frankfurt, Germany
    BMC Cancer 8:391. 2008
    ..Cyclin B1 is very often found to be overexpressed in primary breast and cervical cancer cells as well as in cancer cell lines. Its expression is correlated with the malignancy of gynecological cancers...
  12. ncbi request reprint FHL2 regulates cell cycle-dependent and doxorubicin-induced p21Cip1/Waf1 expression in breast cancer cells
    Bernd T Martin
    Department of Gynecology and Obstetrics, Medical School, J W Goethe University, Frankfurt, Germany
    Cell Cycle 6:1779-88. 2007
    ....
  13. pmc Tumor inhibition by genomically integrated inducible RNAi-cassettes
    Sven Kappel
    Department of Gynecology and Obstetrics, School of Medicine, J W Goethe University, Theodor Stern Kai 7, D 60590 Frankfurt, Germany
    Nucleic Acids Res 34:4527-36. 2006
    ..Taken together, our data revealed that genomically integrated RNAi-elements are suitable to hamper tumor growth by conditional expression of shRNA...
  14. ncbi request reprint Polo-like kinase 1-mediated phosphorylation stabilizes Pin1 by inhibiting its ubiquitination in human cells
    Frank Eckerdt
    Department of Gynecology and Obstetrics, J W Goethe University, Theodor Stern Kai 7, Frankfurt D 60590, Germany
    J Biol Chem 280:36575-83. 2005
    ..Since previous reports suggested that Plk1 is a substrate of Pin1, our work adds a new dimension to this interaction of two important mitotic regulators...
  15. ncbi request reprint Cyclin B1 depletion inhibits proliferation and induces apoptosis in human tumor cells
    Juping Yuan
    Department of Gynaecology and Obstetrics, Medical School, JW Goethe University, Theodor Stern Kai 7, D 60590 Frankfurt, Germany
    Oncogene 23:5843-52. 2004
    ..These results indicate that siRNAs against cyclin B1 could become a powerful antiproliferative tool in future antitumor therapy...
  16. ncbi request reprint Biological impact of freezing Plk1 in its inactive conformation in cancer cells
    Sarah Keppner
    Department of Obstetrics and Gynecology, Medical School, Goethe University, Frankfurt, Germany
    Cell Cycle 9:761-73. 2010
    ..This study suggests that Plk1 kinase inhibitors targeting the inactive conformation of Plk1 may be considered for the development of cancer therapeutics...
  17. pmc Toxicity modelling of Plk1-targeted therapies in genetically engineered mice and cultured primary mammalian cells
    Monika Raab
    Department of Obstetrics and Gynecology, School of Medicine, Johann Wolfgang Goethe University, Theodor Stern Kai 7, 60590 Frankfurt, Germany
    Nat Commun 2:395. 2011
    ..Responses to Plk1-depletion, both in cultured primary cells and in our iKD-mouse model, correspond well and thus provide the basis for using validated iKD mice in predicting responses to therapeutic interventions...
  18. pmc Silencing of the HER2/neu gene by siRNA inhibits proliferation and induces apoptosis in HER2/neu-overexpressing breast cancer cells
    Timo Faltus
    Department of Obstetrics and Gynecology, Medical School, J W Goethe University, Theodor Stern Kai 7, Frankfurt 60590, Germany
    Neoplasia 6:786-95. 2004
    ..Our observations suggest that siRNA targeted against human HER2/neu may be valuable tools as antiproliferative agents that display activity against neoplastic cells at very low doses...
  19. ncbi request reprint Conditional inhibition of cancer cell proliferation by tetracycline-responsive, H1 promoter-driven silencing of PLK1
    Yves Matthess
    Department of Gynecology and Obstetrics, School of Medicine, JW Goethe University, Theodor Stern Kai 7, Haus 15, Frankfurt 60590, Germany
    Oncogene 24:2973-80. 2005
    ..Our data indicate that an inducible transcription system for shRNAs based on the human H1 promoter could be a versatile tool for controlled gene silencing in vitro...
  20. pmc Polo-box domain inhibitor poloxin activates the spindle assembly checkpoint and inhibits tumor growth in vivo
    Juping Yuan
    Department of Gynecology and Obstetrics, School of Medicine, J W Goethe University, Frankfurt, Germany
    Am J Pathol 179:2091-9. 2011
    ..The data highlight that targeting the PBD by Poloxin is a powerful approach for selectively inhibiting Plk1 function in vitro and in vivo...
  21. ncbi request reprint Reduction of cisplatin dosage by ZD 1839
    Markus Hambek
    Department of Otorhonolaryngology, School of Medicine, J W Goethe University, 60590 Frankfurt, Germany
    Anticancer Res 25:3985-8. 2005
    ..Adding ZD 1839 to CDDP may therefore enable CDDP treatment at a lower dose without compromising antiproliferative effects...
  22. ncbi request reprint Cooperative phosphorylation including the activity of polo-like kinase 1 regulates the subcellular localization of cyclin B1
    Juping Yuan
    Department of Obstetrics and Gynecology, JW Goethe University, Theodor Stern Kai 7, D 60590 Frankfurt, Germany
    Oncogene 21:8282-92. 2002
    ..Still, multiple serine mutations are required to prevent nuclear translocation completely indicating that orchestrated phosphorylation within the CRS triggers rapid import of cyclin B1...
  23. ncbi request reprint Efficient internalization of the polo-box of polo-like kinase 1 fused to an Antennapedia peptide results in inhibition of cancer cell proliferation
    Juping Yuan
    Department of Obstetrics and Gynecology, Medical School, J W Goethe University, 60590 Frankfurt, Germany
    Cancer Res 62:4186-90. 2002
    ..The treatment caused mitotic arrest, misaligned chromosomes, and multiple centrosomes. Taken together, membrane-permeable polo-box peptides inhibit cancer cell proliferation efficiently...
  24. pmc Cdk1/cyclin B1 controls Fas-mediated apoptosis by regulating caspase-8 activity
    Yves Matthess
    Department of Obstetrics and Gynecology, School of Medicine, J W Goethe University, Frankfurt, Germany
    Mol Cell Biol 30:5726-40. 2010
    ..Finally, this new mechanism may also contribute to tumorigenesis...
  25. pmc Functional and spatial regulation of mitotic centromere-associated kinesin by cyclin-dependent kinase 1
    Mourad Sanhaji
    Department of Gynecology and Obstetrics, School of Medicine, J W Goethe University, Theodor Stern Kai 7, 60590 Frankfurt, Germany
    Mol Cell Biol 30:2594-607. 2010
    ..This is the first study demonstrating that Cdk1 regulates the localization and activity of MCAK in mitosis by directly phosphorylating the catalytic core domain of MCAK...
  26. ncbi request reprint Silencing of mammalian genes by tetracycline-inducible shRNA expression
    Sven Kappel
    Department of Gynaecology and Obstetrics, School of Medicine, J W Goethe University, Theodor Stern Kai 7, D 60590 Frankfurt Main, Germany
    Nat Protoc 2:3257-69. 2007
    ..The entire protocol (preparation of constructs, generation of stable cell lines and functional analysis) can be completed in 3 months...
  27. ncbi request reprint Downregulation of human polo-like kinase activity by antisense oligonucleotides induces growth inhibition in cancer cells
    Birgit Spänkuch-Schmitt
    Department of Obstetrics and Gynecology, School of Medicine, JW Goethe University, Theodor Stern Kai 7, 60596 Frankfurt, Germany
    Oncogene 21:3162-71. 2002
    ..Considerable antitumor activity was observed in vivo against A549 cells. This study suggests that antisense inhibitors targeted against PLK1 at well tolerated doses may be considered as a cancer therapeutic agent...
  28. ncbi request reprint Polo-like kinases and oncogenesis
    Frank Eckerdt
    Department of Gynecology and Obstetrics, Medical School, JW Goethe University, Theodor Stern Kai 7, Frankfurt D 60590, Germany
    Oncogene 24:267-76. 2005
    ..In this review, we shall discuss the roles of Plks in oncogenesis and Plk1 as a target for therapeutic intervention against cancer...
  29. ncbi request reprint Polo-like kinase 1: target and regulator of transcriptional control
    Bernd T Martin
    Department of Gynecology and Obstetric, Medical School, J W Goethe University, Frankfurt, Germany
    Cell Cycle 5:2881-5. 2006
    ..Furthermore, transcription factors regulated by Plk1 will also be subject of discussion...
  30. ncbi request reprint STAT 3 activation in head and neck squamous cell carcinomas is controlled by the EGFR
    Markus Hambek
    Department of Otorhinolaryngology, School of Medicine, J W Goethe University, 60590 Frankfurt, Germany
    Anticancer Res 24:3881-6. 2004
    ..These findings provide evidence that STAT 3 signal activity in head and neck carcinomas, which is partially responsible for proliferative activity, can be controlled via the EGFR...
  31. ncbi request reprint Demands on caring relatives of head and neck cancer patients
    Mehran Baghi
    Department of Otorhinolaryngology, School of Medicine, J W Goethe University, Frankfurt, Germany
    Laryngoscope 117:712-6. 2007
    ....
  32. ncbi request reprint Expression of polo-like kinase (PLK1) in thin melanomas: a novel marker of metastatic disease
    Lucas Kneisel
    Department of Dermatology, Johann Wolfgang Goethe University, School of Medicine, Theodor Stern Kai 7, 60590 Frankfurt, Germany
    J Cutan Pathol 29:354-8. 2002
    ..However, some thin melanomas (< or= 0.75 mm), which should have an excellent prognosis according to Breslow, can be lethal due to their ability to metastasize...
  33. ncbi request reprint Expression of endothelial and inducible nitric oxide synthase in benign and malignant lesions of the breast and measurement of nitric oxide using electron paramagnetic resonance spectroscopy
    Sibylle Loibl
    Department of Gynecology and Obstetrics, University of Frankfurt, Frankfurt am Main, Germany
    Cancer 95:1191-8. 2002
    ..An increased NO concentration catalyzed by NO synthase (NOS) is cytotoxic and can promote apoptosis. The expression of endothelial NOS (e-NOS) and induced NOS (i-NOS) was examined in various breast tumors...
  34. ncbi request reprint Investigations on the inducible and endothelial nitric oxide synthases in human breast cancer cell line MCF-7 - estrogen has an influence on e-NOS, but not on i-NOS
    Sibylle Loibl
    Department of Gynecology and Obstetrics, University of Frankfurt, Theodor Stern Kai 7 9, 60590 Frankfurt am Main, Germany
    Pathol Res Pract 202:1-7. 2006
    ..In conclusion, e-NOS and i-NOS are weakly expressed in the MCF-7 cell line, but are stimulated differently. The MCF-7 cell may contain both a constitutive NOS and an inducible NOS...
  35. ncbi request reprint The role of early expression of inducible nitric oxide synthase in human breast cancer
    Sibylle Loibl
    Department of Gynaecology and Obstetrics, J W Goethe University of Frankfurt, Theodor Stern Kai 7 9, 60590 Frankfurt am Main, Germany
    Eur J Cancer 41:265-71. 2005
    ..8% versus 67.1%; P=0.049; log-rank test). To date, this is the largest analysis of i-NOS expression in breast cancer patients and the only study to assess survival...
  36. ncbi request reprint pERK 1/2 inhibit Caspase-8 induced apoptosis in cancer cells by phosphorylating it in a cell cycle specific manner
    Ranadip Mandal
    Department of Gynaecology and Obstetrics, Johann Wolfgang Goethe University, Theodor Stern Kai 7, 60590 Frankfurt am Main, Germany
    Mol Oncol . 2013
    ..Taken together, we propose that a combination of Trail and an inhibitor of ERK 1/2 activities could potentially enhance of Trail's effectiveness as an anti-cancer agent in ERK 1/2 hyperactive cancer cells...
  37. ncbi request reprint RNA interference-based gene silencing in mice: the development of a novel therapeutical strategy
    Birgit Spänkuch
    Department of Obstetrics and Gynecology, Medical School, J W Goethe University, Theodor Stern Kai 7, 60590 Frankfurt, Germany
    Curr Pharm Des 11:3405-19. 2005
    ..In summary, multiple lines of evidence indicate that RNAi seems to become a powerful tool for the fight against undesirable gene expression in human diseases...
  38. ncbi request reprint Another look at imatinib mesylate
    Klaus Strebhardt
    Department of Obstetrics and Gynecology, School of Medicine, J W Goethe University, Frankfurt, Germany
    N Engl J Med 355:2481-2. 2006
  39. doi request reprint Inhibition of polo-like kinase 1 by blocking polo-box domain-dependent protein-protein interactions
    Wolfgang Reindl
    Department of Molecular Biology, Max Planck Institute of Biochemistry and Munich Center for Integrated Protein Science CiPS M, Martinsried, Germany
    Chem Biol 15:459-66. 2008
    ..Our data validate the Plk1 PBD as an anticancer target and provide a rationale for developing thymoquinone derivatives as anticancer drugs...
  40. ncbi request reprint Polo-like kinase 1: target and regulator of anaphase-promoting complex/cyclosome-dependent proteolysis
    Frank Eckerdt
    Department of Pharmacology, University of Colorado School of Medicine, Denver, Colorado 80262, USA
    Cancer Res 66:6895-8. 2006
    ..The mechanisms underlying the control of genomic stability by Plk1 are discussed in this review...
  41. ncbi request reprint Trastuzumab-modified nanoparticles: optimisation of preparation and uptake in cancer cells
    Isabel Steinhauser
    Institute for Pharmaceutical Technology, Biocenter of Johann Wolfgang Goethe University, Max von Laue Strasse 9, D 60438 Frankfurt, Germany
    Biomaterials 27:4975-83. 2006
    ..These data provide the basis for the development of stable and biological active carrier systems for directed targeting of tumour cells using trastuzumab-conjugated HSA nanoparticles...
  42. ncbi request reprint Identification of high risk breast-cancer patients by gene expression profiling
    Andre Ahr
    Lancet 359:131-2. 2002
    ..Our analysis identifies breast-cancer patients with a high risk of disease recurrence, and could act as a first step towards improved patient-adapted therapy...
  43. ncbi request reprint Highly specific HER2-mediated cellular uptake of antibody-modified nanoparticles in tumour cells
    Heidrun Wartlick
    Institute for Pharmaceutical Technology, Biocenter of Johann Wolfgang Goethe University, Marie Curie Strasse 9, D 60439 Frankfurt, Germany
    J Drug Target 12:461-71. 2004
    ..To our knowledge, this is the first study that demonstrates the effective and specific targeting of protein-based nanoparticles as drug delivery systems...
  44. ncbi request reprint Antiproliferative activity of bortezomib alone and in combination with cisplatin or docetaxel in head and neck squamous cell carcinoma cell lines
    Jens Wagenblast
    ENT Department, Medical School, Goethe University, Frankfurt am Main, Germany
    J Cancer Res Clin Oncol 134:323-30. 2008
    ....
  45. ncbi request reprint Tumour cell delivery of antisense oligonuclceotides by human serum albumin nanoparticles
    Heidrun Wartlick
    Institute for Pharmaceutical Technology, Biocenter of Johann Wolfgang Goethe University, Marie Curie Strasse 9, D 60439 Frankfurt, Germany
    J Control Release 96:483-95. 2004
    ....