Len Neckers

Summary

Affiliation: National Institutes of Health
Country: USA

Publications

  1. pmc Amplification and high-level expression of heat shock protein 90 marks aggressive phenotypes of human epidermal growth factor receptor 2 negative breast cancer
    Qing Cheng
    Department of Surgery, Duke University Medical Center, Box 2606, 203 Research Drive, Durham, NC 27710, USA
    Breast Cancer Res 14:R62. 2012
  2. pmc Hsp90 molecular chaperone inhibitors: are we there yet?
    Len Neckers
    Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA
    Clin Cancer Res 18:64-76. 2012
  3. pmc Fumarate hydratase deficiency in renal cancer induces glycolytic addiction and hypoxia-inducible transcription factor 1alpha stabilization by glucose-dependent generation of reactive oxygen species
    Sunil Sudarshan
    Urologic Oncology Branch, National Cancer Institute NIH, Bethesda, MD 20892, USA
    Mol Cell Biol 29:4080-90. 2009
  4. pmc Threonine 22 phosphorylation attenuates Hsp90 interaction with cochaperones and affects its chaperone activity
    Mehdi Mollapour
    Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, 9000 Rockville Pike, Bethesda, MD 20892, USA
    Mol Cell 41:672-81. 2011
  5. ncbi request reprint Endoplasmic reticulum vacuolization and valosin-containing protein relocalization result from simultaneous hsp90 inhibition by geldanamycin and proteasome inhibition by velcade
    Edward G Mimnaugh
    Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH, 9000 Rockville Pike, Building 10, Room 1 5940, Bethesda, MD 20892 1107, USA
    Mol Cancer Res 4:667-81. 2006
  6. pmc Dynamic tyrosine phosphorylation modulates cycling of the HSP90-P50(CDC37)-AHA1 chaperone machine
    Wanping Xu
    Urologic Oncology Branch, National Cancer Institute, Bethesda, MD 20892, USA
    Mol Cell 47:434-43. 2012
  7. pmc Loss of Hsp90 association up-regulates Src-dependent ErbB2 activity
    Wanping Xu
    Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, 9000 Rockville Pike, Bethesda, MD 20892 1107, USA
    Mol Cell Biol 27:220-8. 2007
  8. pmc Swe1Wee1-dependent tyrosine phosphorylation of Hsp90 regulates distinct facets of chaperone function
    Mehdi Mollapour
    Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA
    Mol Cell 37:333-43. 2010
  9. pmc TIMP-2 modulates cancer cell transcriptional profile and enhances E-cadherin/beta-catenin complex expression in A549 lung cancer cells
    Dimitra Bourboulia
    Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, Advanced Technology Center, 8717 Grovemont Circle, Bethesda, MD, USA
    Oncotarget 4:163-73. 2013
  10. ncbi request reprint Curcumin is an inhibitor of p300 histone acetylatransferase
    Monica G Marcu
    Urologic Oncology Branch and Medical Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA
    Med Chem 2:169-74. 2006

Detail Information

Publications72

  1. pmc Amplification and high-level expression of heat shock protein 90 marks aggressive phenotypes of human epidermal growth factor receptor 2 negative breast cancer
    Qing Cheng
    Department of Surgery, Duke University Medical Center, Box 2606, 203 Research Drive, Durham, NC 27710, USA
    Breast Cancer Res 14:R62. 2012
    ..Identification of additional molecular factors, especially those characterized by aggressive behavior and poor prognosis, could prioritize interventional opportunities to improve the diagnosis and treatment of breast cancer...
  2. pmc Hsp90 molecular chaperone inhibitors: are we there yet?
    Len Neckers
    Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA
    Clin Cancer Res 18:64-76. 2012
    ..We discuss approaches for enhancing the effectiveness of Hsp90 inhibitors and highlight new chaperone and stress-response pathway targets, including HSF1 and Hsp70...
  3. pmc Fumarate hydratase deficiency in renal cancer induces glycolytic addiction and hypoxia-inducible transcription factor 1alpha stabilization by glucose-dependent generation of reactive oxygen species
    Sunil Sudarshan
    Urologic Oncology Branch, National Cancer Institute NIH, Bethesda, MD 20892, USA
    Mol Cell Biol 29:4080-90. 2009
    ..These data reveal that the obligate glycolytic switch present in HLRCC is critical to HIF stabilization via ROS generation...
  4. pmc Threonine 22 phosphorylation attenuates Hsp90 interaction with cochaperones and affects its chaperone activity
    Mehdi Mollapour
    Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, 9000 Rockville Pike, Bethesda, MD 20892, USA
    Mol Cell 41:672-81. 2011
    ..Overexpression of Aha1 stimulates the ATPase activity, restores cochaperone interactions, and compensates for the functional defects of these Hsp90 mutants...
  5. ncbi request reprint Endoplasmic reticulum vacuolization and valosin-containing protein relocalization result from simultaneous hsp90 inhibition by geldanamycin and proteasome inhibition by velcade
    Edward G Mimnaugh
    Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH, 9000 Rockville Pike, Building 10, Room 1 5940, Bethesda, MD 20892 1107, USA
    Mol Cancer Res 4:667-81. 2006
    ..Thus, simultaneous geldanamycin and Velcade treatment has far-reaching secondary cytotoxic consequences that likely contribute to the cytotoxic activity of this anticancer drug combination...
  6. pmc Dynamic tyrosine phosphorylation modulates cycling of the HSP90-P50(CDC37)-AHA1 chaperone machine
    Wanping Xu
    Urologic Oncology Branch, National Cancer Institute, Bethesda, MD 20892, USA
    Mol Cell 47:434-43. 2012
    ..Finally, at completion of the chaperone cycle, Hsp90 Y627 phosphorylation induces dissociation of the client and remaining cochaperones...
  7. pmc Loss of Hsp90 association up-regulates Src-dependent ErbB2 activity
    Wanping Xu
    Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, 9000 Rockville Pike, Bethesda, MD 20892 1107, USA
    Mol Cell Biol 27:220-8. 2007
    ..These findings suggest that Hsp90 binding to ErbB2 participates in regulation of kinase activity as well as kinase stability...
  8. pmc Swe1Wee1-dependent tyrosine phosphorylation of Hsp90 regulates distinct facets of chaperone function
    Mehdi Mollapour
    Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA
    Mol Cell 37:333-43. 2010
    ....
  9. pmc TIMP-2 modulates cancer cell transcriptional profile and enhances E-cadherin/beta-catenin complex expression in A549 lung cancer cells
    Dimitra Bourboulia
    Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, Advanced Technology Center, 8717 Grovemont Circle, Bethesda, MD, USA
    Oncotarget 4:163-73. 2013
    ..In conclusion, we show that TIMP-2 promotes an anti-tumoral transcriptional profile in vitro and in vivo, including upregulation of E-cadherin, in A549 lung cancer cells. ..
  10. ncbi request reprint Curcumin is an inhibitor of p300 histone acetylatransferase
    Monica G Marcu
    Urologic Oncology Branch and Medical Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA
    Med Chem 2:169-74. 2006
    ..These data thus identify the medicinal natural product curcumin as a novel lead compound for development of possibly therapeutic, p300/CBP-specific HAT inhibitors...
  11. ncbi request reprint HIF overexpression correlates with biallelic loss of fumarate hydratase in renal cancer: novel role of fumarate in regulation of HIF stability
    Jennifer S Isaacs
    Urologic Oncology Branch, National Cancer Institute, Bethesda, Maryland 20892, USA
    Cancer Cell 8:143-53. 2005
    ..Further, we show that fumarate acts as a competitive inhibitor of HPH. These data delineate a novel fumarate-dependent pathway for regulating HPH activity and HIF protein levels...
  12. pmc Combined inhibition of Wee1 and Hsp90 activates intrinsic apoptosis in cancer cells
    Aki Iwai
    Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA
    Cell Cycle 11:3649-55. 2012
    ....
  13. pmc Englerin A stimulates PKCθ to inhibit insulin signaling and to simultaneously activate HSF1: pharmacologically induced synthetic lethality
    Carole Sourbier
    Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Cancer Cell 23:228-37. 2013
    ..By promoting glucose addiction, while simultaneously starving cells of glucose, EA proves to be synthetically lethal to highly glycolytic tumors...
  14. ncbi request reprint The heat shock protein 90 inhibitor geldanamycin and the ErbB inhibitor ZD1839 promote rapid PP1 phosphatase-dependent inactivation of AKT in ErbB2 overexpressing breast cancer cells
    Wanping Xu
    Cell and Cancer Biology Branch, Center for Cancer Research, National Cancer Institute NIH, 9610 Medical Center Drive, Rockville, MD 20850, USA
    Cancer Res 63:7777-84. 2003
    ..ErbB2 thus functions to regulate AKT kinase by simultaneously promoting its activation while inhibiting its inactivation...
  15. pmc Molecular diagnosis and therapy of kidney cancer
    W Marston Linehan
    Urologic Oncology Branch, National Cancer Institute, Bethesda, Maryland 20892, USA
    Annu Rev Med 61:329-43. 2010
    ..Knowledge of these kidney cancer gene pathways has enabled new approaches in the management of this disease and has provided the foundation for the development of targeted therapeutics...
  16. ncbi request reprint IL-1beta-mediated up-regulation of HIF-1alpha via an NFkappaB/COX-2 pathway identifies HIF-1 as a critical link between inflammation and oncogenesis
    Yun Jin Jung
    Cell and Cancer Biology Branch, CCR, National Cancer Institute, 9610 Medical Center Dr, Suite 300, Rockville, Maryland 20850, USA
    FASEB J 17:2115-7. 2003
    ..Thus, HIF-1 is identified as a pivotal transcription factor linking the inflammatory and oncogenic pathways...
  17. ncbi request reprint Cancer cells harboring MET gene amplification activate alternative signaling pathways to escape MET inhibition but remain sensitive to Hsp90 inhibitors
    Suiquan Wang
    Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA
    Cell Cycle 8:2050-6. 2009
    ..In contrast, Hsp90 inhibitors provide long-lasting suppression of c-Met-dependent signaling, and these drugs should be further evaluated in tumors driven by MET gene amplification...
  18. ncbi request reprint Surface charge and hydrophobicity determine ErbB2 binding to the Hsp90 chaperone complex
    Wanping Xu
    Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, Rockville, Maryland 20850, USA
    Nat Struct Mol Biol 12:120-6. 2005
    ..Notably, the immature ErbB2 point mutant remains sensitive to GA, suggesting that mature and nascent client kinases may use distinct motifs to interact with the Hsp90 chaperone complex...
  19. ncbi request reprint The HSP90 inhibitor ganetespib synergizes with the MET kinase inhibitor crizotinib in both crizotinib-sensitive and -resistant MET-driven tumor models
    Naoto Miyajima
    Authors Affiliations Urologic Oncology Branch and Medical Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland Departments of Urology, Biochemistry, and Molecular Biology, Cancer Research Institute, SUNY Upstate Medical University, Syracuse, New York and Department of Urology, Hokkaido University Graduate School of Medicine, Sapporo, Japan
    Cancer Res 73:7022-33. 2013
    ....
  20. pmc Targeting Hsp90 prevents escape of breast cancer cells from tyrosine kinase inhibition
    Itai Pashtan
    Howard Hughes Medical Institute, National Institutes of Health Research Scholars Program, Bethesda, Maryland, USA
    Cell Cycle 7:2936-41. 2008
    ..These data support the continued clinical evaluation of Hsp90 inhibitors in breast cancer...
  21. ncbi request reprint Simultaneous inhibition of hsp 90 and the proteasome promotes protein ubiquitination, causes endoplasmic reticulum-derived cytosolic vacuolization, and enhances antitumor activity
    Edward G Mimnaugh
    Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH, Rockville, Maryland 20850, USA
    Mol Cancer Ther 3:551-66. 2004
    ....
  22. doi request reprint Hsp90 charged-linker truncation reverses the functional consequences of weakened hydrophobic contacts in the N domain
    Shinji Tsutsumi
    Urologic Oncology Branch, National Cancer Institute, Bethesda, Maryland, USA
    Nat Struct Mol Biol 16:1141-7. 2009
    ..These data underscore the importance of beta-strand 8 for Hsp90 function and demonstrate that the functional consequences of weakened hydrophobic contacts in this region are reversed by charged-linker truncation...
  23. pmc Casein kinase 2 phosphorylation of Hsp90 threonine 22 modulates chaperone function and drug sensitivity
    Mehdi Mollapour
    Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA
    Oncotarget 2:407-17. 2011
    ..We also provide evidence that T22 is an important determinant of Hsp90 inhibitor sensitivity in yeast and we show that T22 phosphorylation status contributes to drug sensitivity in vivo...
  24. pmc Increasing reactive oxygen species as a therapeutic approach to treat hereditary leiomyomatosis and renal cell carcinoma
    Carole Sourbier
    Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
    Cell Cycle 9:4183-9. 2010
    ..Increasing tumor ROS with bortezomib in combination with cisplatin represents a novel targeted therapeutic approach to treat advanced HLRCC-associated renal tumors...
  25. doi request reprint Contributions of co-chaperones and post-translational modifications towards Hsp90 drug sensitivity
    Annerleim Walton-Diaz
    Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892 1107, USA
    Future Med Chem 5:1059-71. 2013
    ..Here, the impact of post-translational modifications and co-chaperones on the efficacy of Hsp90 inhibitors are reviewed...
  26. ncbi request reprint Aryl hydrocarbon nuclear translocator (ARNT) promotes oxygen-independent stabilization of hypoxia-inducible factor-1alpha by modulating an Hsp90-dependent regulatory pathway
    Jennifer S Isaacs
    Urologic Oncology Branch, Center for Cancer Research, NCI, National Institutes of Health, Rockville, Maryland 20850, USA
    J Biol Chem 279:16128-35. 2004
    ..These data elucidate novel functions for ARNT and Hsp90 in regulating HIF function and further illustrate that cofactor association may significantly impact upon the sensitivity of Hsp90 clients to chaperone inhibitors...
  27. pmc KIT regulates tyrosine phosphorylation and nuclear localization of beta-catenin in mast cell leukemia
    Tomohiro Kajiguchi
    Urologic Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 1107, United States
    Leuk Res 32:761-70. 2008
    ..Aberrant beta-catenin-driven transcription caused by deregulated KIT may represent a significant new target for treatment of mast cell leukemia...
  28. pmc Hsp90 inhibition transiently activates Src kinase and promotes Src-dependent Akt and Erk activation
    Fumitaka Koga
    Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, Building 10, Room 1 5940, Bethesda, MD 20892 1107, USA
    Proc Natl Acad Sci U S A 103:11318-22. 2006
    ..These data suggest that, under certain circumstances, dual inhibition of Hsp90 and Src may be warranted...
  29. pmc Inhibition of Hsp90 activates osteoclast c-Src signaling and promotes growth of prostate carcinoma cells in bone
    Akihiro Yano
    Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, Building 10, Room 1 5940, Bethesda, MD 20892, USA
    Proc Natl Acad Sci U S A 105:15541-6. 2008
    ....
  30. pmc UOK 262 cell line, fumarate hydratase deficient (FH-/FH-) hereditary leiomyomatosis renal cell carcinoma: in vitro and in vivo model of an aberrant energy metabolic pathway in human cancer
    Youfeng Yang
    Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 10 Center Dr, MSC 1107, Bldg 10 CRC, Room 1 5942, Bethesda, MD 20892 1107
    Cancer Genet Cytogenet 196:45-55. 2010
    ..This tumor model is the embodiment of the Warburg effect. UOK 262 provides a unique in vitro and in vivo preclinical model for studying the bioenergetics of the Warburg effect in human cancer...
  31. ncbi request reprint Identification of the genes for kidney cancer: opportunity for disease-specific targeted therapeutics
    W Marston Linehan
    Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA
    Clin Cancer Res 13:671s-679s. 2007
    ..These Mendelian single-gene syndromes provide a unique opportunity to evaluate the effectiveness of agents that target the VHL, c-Met, BHD, and fumarate hydratase pathways...
  32. pmc Low-penetrant RB allele in small-cell cancer shows geldanamycin instability and discordant expression with mutant ras
    Yoonsoo Park
    Genetics Branch, Center for Cancer Research, National Cancer Institute and National Naval Medical Center, Bethesda, Maryland 20889, USA
    Cell Cycle 7:2384-91. 2008
    ..In addition, these data suggest that reversible protein instability and the requirement for a cooperating mutation may provide a stochastic explanation for the molecular basis of incomplete penetrance in kindreds carrying these alleles...
  33. pmc Asymmetric Hsp90 N domain SUMOylation recruits Aha1 and ATP-competitive inhibitors
    Mehdi Mollapour
    Department of Urology, SUNY Upstate Medical University, 750 East Adams Street, Syracuse, NY 13210, USA Department of Biochemistry and Molecular Biology, SUNY Upstate Medical University, 750 East Adams Street, Syracuse, NY 13210, USA Cancer Research Institute, SUNY Upstate Medical University, 750 East Adams Street, Syracuse, NY 13210, USA Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, 9000 Rockville Pike, Bethesda, MD 20892, USA Electronic address
    Mol Cell 53:317-29. 2014
    ....
  34. ncbi request reprint A novel form of mastocytosis associated with a transmembrane c-kit mutation and response to imatinib
    Cem Akin
    Laboratory of Allergic Diseases, National Instititute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Blood 103:3222-5. 2004
    ....
  35. ncbi request reprint Targeting the dynamic HSP90 complex in cancer
    Jane Trepel
    Medical Oncology Branch Center for Cancer Research, National Cancer Institute, Building 10, Room 1 5940, 9000 Rockville Pike, Bethesda, MD 20892, USA
    Nat Rev Cancer 10:537-49. 2010
    ....
  36. pmc Hereditary kidney cancer: unique opportunity for disease-based therapy
    W Marston Linehan
    Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, Building 10 CRC, Room 1 5940, Bethesda, MD 20892 1107, USA
    Cancer 115:2252-61. 2009
    ..Studies of the tricarboxylic acid cycle and the VHL-HIF pathways have provided the foundation for therapeutic approaches in patients with HLRCC-associated kidney cancer as well as other hereditary and sporadic forms of RCC...
  37. ncbi request reprint Hsp90 phosphorylation, Wee1 and the cell cycle
    Mehdi Mollapour
    Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA
    Cell Cycle 9:2310-6. 2010
    ..These findings demonstrate the importance of Hsp90 phosphorylation for proper cell cycle regulation...
  38. ncbi request reprint TIMP-2 modulates cancer cell transcriptional profile and enhances E-cadherin/beta-catenin complex expression in A549 lung cancer cells
    Dimitra Bourboulia
    Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, Advanced Technology Center, 8717 Grovemont Circle, Bethesda, MD, USA
    Oncotarget 4:166-76. 2013
    ..In conclusion, we show that TIMP-2 promotes an anti-tumoral transcriptional profile in vitro and in vivo, including upregulation of E-cadherin, in A549 lung cancer cells...
  39. pmc Mitochondrial topoisomerase I is critical for mitochondrial integrity and cellular energy metabolism
    Céline Douarre
    Laboratory of Molecular Pharmacology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America
    PLoS ONE 7:e41094. 2012
    ..Relaxation of the circular, double-stranded mtDNA relies on the presence of topoisomerase activity. Three different topoisomerases have been identified in mitochondria: Top1mt, Top3α and a truncated form of Top2β...
  40. ncbi request reprint Genetic basis of cancer of the kidney: disease-specific approaches to therapy
    W Marston Linehan
    Urologic Oncology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892 1501, USA
    Clin Cancer Res 10:6282S-9S. 2004
    ..The HLRC gene has been found to be the Krebs cycle enzyme, fumarate hydratase. Studies are under way to understand the downstream pathway of this cancer gene...
  41. ncbi request reprint Using natural product inhibitors to validate Hsp90 as a molecular target in cancer
    Len Neckers
    Urologic Oncology Branch, National Cancer Institute, NIH, 9000 Rockville Pike, Building 10, Room 1 5940, Bethesda, MD 20892 1107, USA
    Curr Top Med Chem 6:1163-71. 2006
    ..Small molecule inhibitors of Hsp90 have been very useful in understanding Hsp90 biology and in validating this protein as a molecular target for anti-cancer drug development...
  42. pmc An acetylation site in the middle domain of Hsp90 regulates chaperone function
    Bradley T Scroggins
    Urologic Oncology Branch, National Cancer Institute, Bethesda, MD 20892, USA
    Mol Cell 25:151-9. 2007
    ..These data suggest that acetylation/deacetylation of K294 plays an important role in regulating the Hsp90 chaperone cycle...
  43. ncbi request reprint Mechanisms of disease: hereditary leiomyomatosis and renal cell cancer--a distinct form of hereditary kidney cancer
    Sunil Sudarshan
    Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892 1107, USA
    Nat Clin Pract Urol 4:104-10. 2007
    ..Nevertheless, continued investigation of HLRCC should provide further insight into the mechanisms of kidney cancer development, and could potentially identify targets for new therapeutic approaches to RCC...
  44. pmc Methoxychalcone inhibitors of androgen receptor translocation and function
    Yeong Sang Kim
    Medical Oncology Branch, National Cancer Institute, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, United States
    Bioorg Med Chem Lett 22:2105-9. 2012
    ....
  45. doi request reprint Detecting HSP90 phosphorylation
    Mehdi Mollapour
    Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
    Methods Mol Biol 787:67-74. 2011
    ..Yeast can be used to express and purify HSP90 and also detect its phosphorylation by pan-phosphoserine or phosphothreonine antibodies...
  46. ncbi request reprint Targeting the molecular chaperone heat shock protein 90 provides a multifaceted effect on diverse cell signaling pathways of cancer cells
    Wanping Xu
    Urologic Oncology Branch, National Cancer Institute, Bethesda, MD 20892 1107, USA
    Clin Cancer Res 13:1625-9. 2007
  47. ncbi request reprint Heat shock protein 90
    Len Neckers
    Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Rockville, Maryland 20850, USA
    Curr Opin Oncol 15:419-24. 2003
    ..Hsp90 inhibitors are unique in that, although they are directed towards a specific molecular target, they simultaneously inhibit multiple signaling pathways that frequently interact to promote cancer cell survival...
  48. ncbi request reprint Pseudohypoxic pathways in renal cell carcinoma
    Gennady Bratslavsky
    Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892 1107, USA
    Clin Cancer Res 13:4667-71. 2007
    ..Understanding of these pseudohypoxic pathways has provided a better appreciation of the molecular mechanisms of carcinogenesis in addition to providing a rationale for targeted therapeutic approaches...
  49. pmc Impact of heat-shock protein 90 on cancer metastasis
    Shinji Tsutsumi
    Urologic Oncology Branch, National Cancer Institute, NIH, Bethesda, MD 20892 1107, USA
    Future Oncol 5:679-88. 2009
    ..In this review, we will highlight the importance of Hsp90 in cancer metastasis and the therapeutic potential of Hsp90 inhibitors as antimetastasis drugs...
  50. ncbi request reprint Modulation of p53, ErbB1, ErbB2, and Raf-1 expression in lung cancer cells by depsipeptide FR901228
    Xiaodan Yu
    Thoracic Oncology Section, Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
    J Natl Cancer Inst 94:504-13. 2002
    ..This study evaluated the mechanisms by which FK228 mediates apoptosis in non-small-cell lung cancer (NSCLC) cells...
  51. pmc Post-translational modifications of Hsp90 and their contributions to chaperone regulation
    Mehdi Mollapour
    National Cancer Institute, Bethesda, MD, USA
    Biochim Biophys Acta 1823:648-55. 2012
    ..This article is part of a Special Issue entitled: Heat Shock Protein 90 (HSP90)...
  52. ncbi request reprint 17-Allylamino-17-demethoxygeldanamycin (17-AAG) is effective in down-regulating mutated, constitutively activated KIT protein in human mast cells
    Gerard Fumo
    National Cancer Institute, Cell and Cancer Biology Branch, 9610 Medical Center Dr, Ste 300, Rockville, MD 20850, USA
    Blood 103:1078-84. 2004
    ..These data provide compelling evidence that 17-AAG may be effective in the treatment of c-kit-related diseases including mastocytosis, GISTs, mast cell leukemia, subtypes of acute myelogenous leukemia, and testicular cancer...
  53. ncbi request reprint Extracellular heat shock protein 90: a role for a molecular chaperone in cell motility and cancer metastasis
    Shinji Tsutsumi
    Urologic Oncology Branch, National Cancer Institute, 9000 Rockville Pike, Building 10 CRC, 1 5940, Bethesda, MD 20892, USA
    Cancer Sci 98:1536-9. 2007
    ..In addition, because cell-surface Hsp90 may be the point of contact between some viruses and host cells, this pool of the chaperone may play a distinct role in initiation of infectious disease...
  54. ncbi request reprint Hsp90 inhibitors as novel cancer chemotherapeutic agents
    Len Neckers
    Cell and Cancer Biology Branch, National Cancer Institute, National Institutes of Health, 9610 Medical Center Drive, Suite 300, Rockville, MD 20850, USA
    Trends Mol Med 8:S55-61. 2002
    ..Because of the chemoprotective activity of several proteins that are Hsp90 clients, the combination of an Hsp90 inhibitor with a standard chemotherapeutic agent could dramatically increase the in vivo efficacy of the therapeutic agent...
  55. ncbi request reprint Heat shock protein 90 inhibition by 17-allylamino-17- demethoxygeldanamycin: a novel therapeutic approach for treating hormone-refractory prostate cancer
    Len Neckers
    Cell and Cancer Biology Branch, National Cancer Institute, Rockville, Maryland 20850, USA
    Clin Cancer Res 8:962-6. 2002
  56. ncbi request reprint Quantum chemical calculations and mutational analysis suggest heat shock protein 90 catalyzes trans-cis isomerization of geldanamycin
    Yong Sok Lee
    Center for Molecular Modeling, Center for Information Technology, National Institutes of Health, Building 12A, Room 2049, Bethesda, Maryland 20892, USA
    Chem Biol 11:991-8. 2004
    ..The added requirement of isomerization prior to tight binding may explain the enhanced binding affinity of GA for HSP90 in a cell extract versus in a purified form...
  57. pmc Phase I trial of 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG), a heat shock protein inhibitor, administered twice weekly in patients with advanced malignancies
    Shivaani Kummar
    Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA
    Eur J Cancer 46:340-7. 2010
    ....
  58. doi request reprint The complex dance of the molecular chaperone Hsp90
    Len Neckers
    Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA
    Trends Biochem Sci 34:223-6. 2009
    ..The conformational program of Hsp90 is conserved from bacteria to humans, although the population dynamics are species specific...
  59. ncbi request reprint Development of small molecule Hsp90 inhibitors: utilizing both forward and reverse chemical genomics for drug identification
    Len Neckers
    Cell and Cancer Biology Branch, National Cancer Institute, NIH, Rockville, MD 20850, USA
    Curr Med Chem 10:733-9. 2003
    ..Small molecule inhibitors of Hsp90 have been very useful in understanding Hsp90 biology and in validating this protein as a molecular target for anti-cancer drug development...
  60. ncbi request reprint Heat shock protein 90 as a molecular target for cancer therapeutics
    Jennifer S Isaacs
    Cell and Cancer Biology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Rockville, MD 20850, USA
    Cancer Cell 3:213-7. 2003
  61. pmc Tumour necrosis factor receptor 1 mediates endoplasmic reticulum stress-induced activation of the MAP kinase JNK
    QingFeng Yang
    Cell and Cancer Biology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, Bethesda, Maryland 20892, USA
    EMBO Rep 7:622-7. 2006
    ..We also found that TNFR1 functions downstream of IRE1 and that IRE1 is present in the same complex with TNFR1 under ER stress condition. Therefore, our study shows a novel role of TNFR1 in mediating ER stress-induced JNK activation...
  62. ncbi request reprint Heat-shock protein 90 inhibitors as novel cancer chemotherapeutics - an update
    Len Neckers
    National Cancer Institute, Urologic Oncology Branch, 9610 Medical Ctr, Suite 300, Rockville, MD 20850, USA
    Expert Opin Emerg Drugs 10:137-49. 2005
    ..Other Hsp90 inhibitors are either in Phase I clinical trial or under development. This update will focus on how the latest developments in Hsp90 biology may better inform the clinical development of Hsp90 inhibitors...
  63. ncbi request reprint Heat shock protein 90: the cancer chaperone
    Len Neckers
    Urologic Oncology Branch, National Cancer Institute, Bethesda, MD 20892, USA
    J Biosci 32:517-30. 2007
    ....
  64. pmc Ras, ROS and proteotoxic stress: a delicate balance
    Wanping Xu
    Urologic Oncology Branch, National Cancer Institute, Center for Cancer Research, Bethesda, MD 20892, USA
    Cancer Cell 20:281-2. 2011
    ..In this issue of Cancer Cell, De Raedt et al. identify a novel strategy that utilizes this dependency to cause cell death...
  65. ncbi request reprint Hsp90 inhibitors disrupt mitochondrial homeostasis in cancer cells
    Len Neckers
    Urologic Oncology Branch, Center for Cancer Research, NCI, 9000 Rockville Pike, Bldg 10 CRC, Room 1 5940, Bethesda, MD 20892, USA
    Chem Biol 14:1204-6. 2007
    ..now identifies the molecular components of the proapoptotic network regulated by TRAP1, that includes Hsp90. Targeting Hsp90/TRAP1 inhibitors to mitochondria induces rapid tumor cell-specific apoptosis...
  66. doi request reprint Post-translational modification of heat-shock protein 90: impact on chaperone function
    Bradley T Scroggins
    National Cancer Institute, Urologic Oncology Branch, Bldg 10 CRC, Room 1 5940, 9000 Rockville Pike, Bethesda, MD 20892, USA 1 301 496 5899 1 301 402 0922
    Expert Opin Drug Discov 2:1403-14. 2007
    ....
  67. pmc The double edge of the HSP90-CDC37 chaperone machinery: opposing determinants of kinase stability and activity
    Wanping Xu
    Urologic Oncology Branch, National Cancer Institute, Bethesda, MD, USA
    Future Oncol 8:939-42. 2012
    ..These data emphasize the versatile roles of molecular chaperones associated with LKB1 and warrant future studies to characterize the clinical relevance of these observations...
  68. pmc The exception that reinforces the rule: crosspriming by cytosolic peptides that escape degradation
    Avital Lev
    Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Immunity 28:787-98. 2008
    ....
  69. ncbi request reprint Microtubule disruption utilizes an NFkappa B-dependent pathway to stabilize HIF-1alpha protein
    Yun Jin Jung
    Cell and Cancer Biology Branch, Center for Cancer Research, NCI, National Institutes of Health, Rockville, Maryland 20850, USA
    J Biol Chem 278:7445-52. 2003
    ..Collectively, these data support a model in which NFkappaB is a focal point for the convergence of MDA-mediated signaling events leading to HIF-1 induction, thus revealing a novel aspect of HIF-1alpha regulation and function...
  70. ncbi request reprint Epithelial-directed drug delivery: influence of formulation and delivery devices
    James L Mulshine
    Department of Health and Human Services, Cell and Cancer Biology Branch, Center for Cancer Research, National Cancer Institute, National Institutes for Health, Room 12N226, Bethesda, MD 20892 1906, USA
    Lung Cancer 46:387-92. 2004
    ..The questions considered in this forum is whether improvements in these areas are sufficiently mature to allow application of local regional drug delivery with targeted drug agents to improve the management of early lung cancer...
  71. pmc Molecular chaperones in pathogen virulence: emerging new targets for therapy
    Len Neckers
    Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892 1107, USA
    Cell Host Microbe 4:519-27. 2008
    ..In addition to discussing ingenious ways by which pathogens have utilized chaperones, the potential of exploiting pathogen chaperones as drug targets is also discussed...
  72. ncbi request reprint Screening for inducers of kinase degradation
    Len Neckers
    Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, 9610 Medical Center Drive, Rockville, MD 20850, USA
    Chem Biol 10:587-9. 2003
    ..In this issue, researchers describe a simple assay for the rapid, high-throughput identification of novel agents that promote degradation of the kinases Her2 and EGFR...