Avi Ashkenazi

Summary

Affiliation: Genentech Inc
Country: USA

Publications

  1. doi request reprint Ligand-based targeting of apoptosis in cancer: the potential of recombinant human apoptosis ligand 2/Tumor necrosis factor-related apoptosis-inducing ligand (rhApo2L/TRAIL)
    Avi Ashkenazi
    Department of Molecular Oncology, Genentech Inc, South San Francisco, CA 94080, USA
    J Clin Oncol 26:3621-30. 2008
  2. doi request reprint TRAF2 Sets a threshold for extrinsic apoptosis by tagging caspase-8 with a ubiquitin shutoff timer
    Francois Gonzalvez
    Department of Molecular Oncology, Genentech Inc, South San Francisco, CA 94080, USA
    Mol Cell 48:888-99. 2012
  3. doi request reprint Inflammasome-dependent and -independent IL-18 production mediates immunity to the ISCOMATRIX adjuvant
    Nicholas S Wilson
    Cancer Immunology, Genentech, Inc, South San Francisco, CA 94080
    J Immunol 192:3259-68. 2014
  4. doi request reprint An Fcγ receptor-dependent mechanism drives antibody-mediated target-receptor signaling in cancer cells
    Nicholas S Wilson
    Department of Molecular Oncology, Genentech, Inc, 1 DNA Way, South San Francisco, CA 94080, USA
    Cancer Cell 19:101-13. 2011
  5. doi request reprint Cooperation of the agonistic DR5 antibody apomab with chemotherapy to inhibit orthotopic lung tumor growth and improve survival
    Hongkui Jin
    Department of Translational Oncology, Genentech, Inc, South San Francisco, California 94080, USA
    Clin Cancer Res 14:7733-40. 2008
  6. pmc Opposing unfolded-protein-response signals converge on death receptor 5 to control apoptosis
    Min Lu
    Cancer Immunology, Genentech, Inc, 1 DNA Way, South San Francisco, CA 94080, USA
    Science 345:98-101. 2014
  7. pmc X chromosome-linked inhibitor of apoptosis regulates cell death induction by proapoptotic receptor agonists
    Eugene Varfolomeev
    Department of Protein Engineering, Genentech, Inc, South San Francisco, California 94080, USA
    J Biol Chem 284:34553-60. 2009
  8. doi request reprint Proapoptotic activation of death receptor 5 on tumor endothelial cells disrupts the vasculature and reduces tumor growth
    Nicholas S Wilson
    Department of Molecular Oncology, Genentech, Inc, South San Francisco, CA 94080, USA
    Cancer Cell 22:80-90. 2012
  9. doi request reprint Antixenograft tumor activity of a humanized anti-insulin-like growth factor-I receptor monoclonal antibody is associated with decreased AKT activation and glucose uptake
    Yonglei Shang
    Genentech, Inc, South San Francisco, California, USA
    Mol Cancer Ther 7:2599-608. 2008
  10. pmc Antibody-based targeting of FGFR3 in bladder carcinoma and t(4;14)-positive multiple myeloma in mice
    Jing Qing
    Department of Molecular Oncology, Genentech Inc, South San Francisco, California, USA
    J Clin Invest 119:1216-29. 2009

Collaborators

Detail Information

Publications50

  1. doi request reprint Ligand-based targeting of apoptosis in cancer: the potential of recombinant human apoptosis ligand 2/Tumor necrosis factor-related apoptosis-inducing ligand (rhApo2L/TRAIL)
    Avi Ashkenazi
    Department of Molecular Oncology, Genentech Inc, South San Francisco, CA 94080, USA
    J Clin Oncol 26:3621-30. 2008
    ..Clinical studies are ongoing to assess the safety and efficacy of this novel agent in combination with established anticancer therapies...
  2. doi request reprint TRAF2 Sets a threshold for extrinsic apoptosis by tagging caspase-8 with a ubiquitin shutoff timer
    Francois Gonzalvez
    Department of Molecular Oncology, Genentech Inc, South San Francisco, CA 94080, USA
    Mol Cell 48:888-99. 2012
    ..Thus, TRAF2 sets a critical barrier for cell-extrinsic apoptosis commitment by tagging activated caspase-8 with a K48-ubiquitin shutoff timer. These results may have important implications for caspase regulation mechanisms...
  3. doi request reprint Inflammasome-dependent and -independent IL-18 production mediates immunity to the ISCOMATRIX adjuvant
    Nicholas S Wilson
    Cancer Immunology, Genentech, Inc, South San Francisco, CA 94080
    J Immunol 192:3259-68. 2014
    ..Taken together, our findings highlight an important disconnect between the mechanisms of vaccine adjuvant action in vitro versus in vivo. ..
  4. doi request reprint An Fcγ receptor-dependent mechanism drives antibody-mediated target-receptor signaling in cancer cells
    Nicholas S Wilson
    Department of Molecular Oncology, Genentech, Inc, 1 DNA Way, South San Francisco, CA 94080, USA
    Cancer Cell 19:101-13. 2011
    ..A CD40-agonistic antibody required similar FcγR interactions to stimulate nuclear factor-κB activity in B cells. Thus, FcγRs can drive antibody-mediated receptor signaling in target cells...
  5. doi request reprint Cooperation of the agonistic DR5 antibody apomab with chemotherapy to inhibit orthotopic lung tumor growth and improve survival
    Hongkui Jin
    Department of Translational Oncology, Genentech, Inc, South San Francisco, California 94080, USA
    Clin Cancer Res 14:7733-40. 2008
    ..Several lung cancer cell lines express DR5 and exhibit apoptosis in response to apomab in vitro...
  6. pmc Opposing unfolded-protein-response signals converge on death receptor 5 to control apoptosis
    Min Lu
    Cancer Immunology, Genentech, Inc, 1 DNA Way, South San Francisco, CA 94080, USA
    Science 345:98-101. 2014
    ..Persistent ER stress built up intracellular DR5 protein, driving ligand-independent DR5 activation and apoptosis engagement via caspase-8. Thus, DR5 integrates opposing UPR signals to couple ER stress and apoptotic cell fate. ..
  7. pmc X chromosome-linked inhibitor of apoptosis regulates cell death induction by proapoptotic receptor agonists
    Eugene Varfolomeev
    Department of Protein Engineering, Genentech, Inc, South San Francisco, California 94080, USA
    J Biol Chem 284:34553-60. 2009
    ....
  8. doi request reprint Proapoptotic activation of death receptor 5 on tumor endothelial cells disrupts the vasculature and reduces tumor growth
    Nicholas S Wilson
    Department of Molecular Oncology, Genentech, Inc, South San Francisco, CA 94080, USA
    Cancer Cell 22:80-90. 2012
    ....
  9. doi request reprint Antixenograft tumor activity of a humanized anti-insulin-like growth factor-I receptor monoclonal antibody is associated with decreased AKT activation and glucose uptake
    Yonglei Shang
    Genentech, Inc, South San Francisco, California, USA
    Mol Cancer Ther 7:2599-608. 2008
    ....
  10. pmc Antibody-based targeting of FGFR3 in bladder carcinoma and t(4;14)-positive multiple myeloma in mice
    Jing Qing
    Department of Molecular Oncology, Genentech Inc, South San Francisco, California, USA
    J Clin Invest 119:1216-29. 2009
    ..These studies provide in vivo evidence demonstrating an oncogenic role of FGFR3 in bladder cancer and support antibody-based targeting of FGFR3 in hematologic and epithelial cancers driven by WT or mutant FGFR3...
  11. ncbi request reprint Molecular determinants of kinase pathway activation by Apo2 ligand/tumor necrosis factor-related apoptosis-inducing ligand
    Eugene Varfolomeev
    Department of Molecular Oncology, Genentech, Inc, South San Francisco, California 94080, USA
    J Biol Chem 280:40599-608. 2005
    ..One function of kinase stimulation by Apo2L/TRAIL may be to promote phagocytic engulfment of apoptotic cells...
  12. pmc TWEAK induces apoptosis through a death-signaling complex comprising receptor-interacting protein 1 (RIP1), Fas-associated death domain (FADD), and caspase-8
    Aminah Ikner
    Department of Molecular Oncology, Genentech, South San Francisco, California 94080, USA
    J Biol Chem 286:21546-54. 2011
    ..The proapoptotic activity of TWEAK is modulated by cIAP1 and CYLD and engages both the extrinsic and intrinsic signaling pathways...
  13. doi request reprint NEMO and RIP1 control cell fate in response to extensive DNA damage via TNF-α feedforward signaling
    Sharon Biton
    Department of Molecular Oncology, Genentech, 1 DNA Way, South San Francisco, CA 94080, USA
    Cell 145:92-103. 2011
    ..Thus, in the context of excessive DNA damage, ATM employs NEMO and RIP1 kinase through autocrine TNF-α signaling to switch on cytokine production and caspase activation. These results shed light on cell-fate regulation by ATM...
  14. doi request reprint Development of immunohistochemistry assays to assess GALNT14 and FUT3/6 in clinical trials of dulanermin and drozitumab
    Howard M Stern
    Departments of Research Pathology, Development Oncology Diagnostics, and Molecular Oncology, Genentech, Inc, South San Francisco, California, USA
    Clin Cancer Res 16:1587-96. 2010
    ....
  15. ncbi request reprint Tumor-cell resistance to death receptor--induced apoptosis through mutational inactivation of the proapoptotic Bcl-2 homolog Bax
    Heidi LeBlanc
    Department of Molecular Oncology, Genentech, South San Francisco, California, USA
    Nat Med 8:274-81. 2002
    ..Thus, Bax mutation in mismatch repair--deficient tumors can cause resistance to death receptor--targeted therapy, but pre-exposure to chemotherapy rescues tumor sensitivity...
  16. ncbi request reprint Cooperation of the proapoptotic receptor agonist rhApo2L/TRAIL with the CD20 antibody rituximab against non-Hodgkin lymphoma xenografts
    Dylan Daniel
    Department of Molecular Oncology, Genentech, South San Francisco, CA 94080, USA
    Blood 110:4037-46. 2007
    ..These findings provide a strong rationale for clinical investigation of rhApo2L/TRAIL in combination with rituximab as a novel strategy for NHL therapy...
  17. pmc Host genetic background impacts modulation of the TLR4 pathway by RON in tissue-associated macrophages
    Amitabha Chaudhuri
    Department of Molecular Oncology, Genentech Inc, South San Francisco, CA 94080, USA
    Immunol Cell Biol 91:451-60. 2013
    ..These findings provide novel insight into the complex interplay between genetic context and immune function. ..
  18. doi request reprint FGFR3 stimulates stearoyl CoA desaturase 1 activity to promote bladder tumor growth
    Xiangnan Du
    Molecular Oncology, Cancer Signaling and Translational Oncology, Bioinformatics, and Pathology, Genentech, Inc, South San Francisco, California 94080, USA
    Cancer Res 72:5843-55. 2012
    ..Together, these findings reveal a previously unrecognized role of FGFR3 in regulating lipid metabolism to maintain tumor growth and survival, and also identify SCD1 as a potential therapeutic target for FGFR3-driven bladder cancer...
  19. pmc Death-receptor activation halts clathrin-dependent endocytosis
    Cary D Austin
    Department of Research Administration, Genentech, Inc, South San Francisco, CA 94080, USA
    Proc Natl Acad Sci U S A 103:10283-8. 2006
    ..Thus, DR-triggered caspase activity disrupts clathrin-dependent endocytosis, leading to amplification of programmed cell death...
  20. doi request reprint Cullin3-based polyubiquitination and p62-dependent aggregation of caspase-8 mediate extrinsic apoptosis signaling
    Zhaoyu Jin
    Department of Molecular Oncology, Genentech, Inc, 1 DNA Way, South San Francisco, CA 94080, USA
    Cell 137:721-35. 2009
    ..These results identify a mechanism that positively controls apoptosis signaling by polyubiquitination and aggregation of a key initiator caspase...
  21. ncbi request reprint Death-receptor O-glycosylation controls tumor-cell sensitivity to the proapoptotic ligand Apo2L/TRAIL
    Klaus W Wagner
    Department of Molecular Diagnostics, Genentech, Inc, 1 DNA Way, South San Francisco, California 94080, USA
    Nat Med 13:1070-7. 2007
    ..These results uncover a new link between death-receptor O-glycosylation and apoptotic signaling, providing potential predictive biomarkers for Apo2L/TRAIL-based cancer therapy...
  22. ncbi request reprint Apo2 ligand/tumor necrosis factor-related apoptosis-inducing ligand cooperates with chemotherapy to inhibit orthotopic lung tumor growth and improve survival
    Hongkui Jin
    Department of Molecular Oncology, Genentech Inc, 1 DNA Way, South San Francisco, CA 94080, USA
    Cancer Res 64:4900-5. 2004
    ..035). These studies provide evidence for in vivo activity of Apo2L/TRAIL against lung tumor xenografts and underscore the potential of this ligand for advancing current lung cancer treatment strategies...
  23. pmc MET Suppresses Epithelial VEGFR2 via Intracrine VEGF-induced Endoplasmic Reticulum-associated Degradation
    Tom T Chen
    Cancer Immunology, Genentech, Inc 1 DNA Way, South San Francisco, CA 94080, USA
    EBioMedicine 2:406-20. 2015
    ..Furthermore, these results suggest rational combinatorial strategies for targeting RTK signaling pathways more effectively, which has potentially important implications for cancer therapy. ..
  24. pmc Distinct involvement of the Gab1 and Grb2 adaptor proteins in signal transduction by the related receptor tyrosine kinases RON and MET
    Amitabha Chaudhuri
    Department of Molecular Oncology, Genentech, Inc, South San Francisco, California 94080, USA
    J Biol Chem 286:32762-74. 2011
    ..Hence, RON and MET differ in their adaptor interactions; furthermore, Grb2 performs a novel antagonistic role in the context of RON signaling...
  25. ncbi request reprint TWEAK attenuates the transition from innate to adaptive immunity
    Heather Maecker
    Department of Molecular Oncology, Genentech, Inc, 1 DNA Way, South San Francisco, CA 94080, USA
    Cell 123:931-44. 2005
    ..Thus, TWEAK suppresses production of IFN-gamma and IL-12, curtailing the innate response and its transition to adaptive TH1 immunity...
  26. ncbi request reprint Targeting death receptors in cancer with Apo2L/TRAIL
    Sean K Kelley
    Genentech Inc, 1 DNA Way, South San Francisco, California 94080, USA
    Curr Opin Pharmacol 4:333-9. 2004
    ..Thus, Apo2L/TRAIL might be effective against tumors that have acquired resistance to conventional therapy, and could augment the efficacy of current treatment in a wide spectrum of cancers...
  27. ncbi request reprint Receptor-selective mutants of apoptosis-inducing ligand 2/tumor necrosis factor-related apoptosis-inducing ligand reveal a greater contribution of death receptor (DR) 5 than DR4 to apoptosis signaling
    Robert F Kelley
    Department of Protein Engineering, Genentech, Inc, South San Francisco, California 94080, USA
    J Biol Chem 280:2205-12. 2005
    ..These results suggest that DR5 may contribute more than DR4 to Apo2L/TRAIL-induced apoptosis in cancer cells that express both death receptors...
  28. ncbi request reprint Targeting death and decoy receptors of the tumour-necrosis factor superfamily
    Avi Ashkenazi
    Department of Molecular Oncology, Genentech, Inc, 1 DNA Way, South San Francisco, California 94080, USA
    Nat Rev Cancer 2:420-30. 2002
  29. doi request reprint Proapoptotic DR4 and DR5 signaling in cancer cells: toward clinical translation
    Annie Yang
    Genentech Inc, 1 DNA Way, South San Francisco, CA 94080, USA
    Curr Opin Cell Biol 22:837-44. 2010
    ..Here we review the molecular and biological determinants of responsiveness to PARAs in cancer cells, and discuss the potential for predictive biomarkers and drug combination strategies to maximize the anti-tumor activity of these agents...
  30. doi request reprint Death receptor signal transducers: nodes of coordination in immune signaling networks
    Nicholas S Wilson
    Genentech, Inc, South San Francisco, California, USA
    Nat Immunol 10:348-55. 2009
    ..Thus, DR signal transducers may provide important nodes of coordination in immune signaling networks...
  31. pmc ISCOMATRIX vaccines mediate CD8+ T-cell cross-priming by a MyD88-dependent signaling pathway
    Nicholas S Wilson
    Department of Molecular Oncology, Genentech Inc, South San Francisco, CA 94080, USA
    Immunol Cell Biol 90:540-52. 2012
    ..Taken together, our findings support the utility of the ISCOMATRIX adjuvant for use in the development of novel vaccines, particularly those requiring strong CD8(+) T-cell immune responses, such as therapeutic cancer vaccines...
  32. doi request reprint Complementary proteomic tools for the dissection of apoptotic proteolysis events
    Victoria C Pham
    Department of Protein Chemistry, Genentech Inc, 1 DNA Way, South San Francisco, California 94080, USA
    J Proteome Res 11:2947-54. 2012
    ....
  33. doi request reprint Targeting the extrinsic apoptosis pathway in cancer
    Avi Ashkenazi
    Department of Molecular Oncology, Genentech Inc, 1 DNA Way, South San Francisco, CA 94080 4990, United States
    Cytokine Growth Factor Rev 19:325-31. 2008
    ..Initial data on rhApo2L/TRAIL and Apomab from phase 1 safety trials also confirm that these agents are suitable for further clinical investigation...
  34. ncbi request reprint Activation of the proapoptotic death receptor DR5 by oligomeric peptide and antibody agonists
    Bing Li
    Department of Protein Engineering, Genentech Inc, 1 DNA Way, South San Francisco, CA 94080, USA
    J Mol Biol 361:522-36. 2006
    ..These phage-derived ligands may be useful for elucidating DR5 activation at the molecular level and for creating synthetic agonists of proapoptotic death receptors...
  35. pmc Fcγ receptors enable anticancer action of proapoptotic and immune-modulatory antibodies
    Jeong M Kim
    Department of Cancer Immunotherapy and Hematology, Genentech Inc, South San Francisco, CA 94080, USA
    J Exp Med 210:1647-51. 2013
    ..Here, we outline a conceptual framework for understanding these findings and discuss their mechanistic and translational implications. ..
  36. doi request reprint Directing cancer cells to self-destruct with pro-apoptotic receptor agonists
    Avi Ashkenazi
    Department of Molecular Oncology, Genentech Inc, 1 DNA Way, South San Francisco, California 94080 4918, USA
    Nat Rev Drug Discov 7:1001-12. 2008
    ..Acting alone, or in concert with other agents, PARAs may overcome key apoptosis blocks and direct cancer cells to self-destruct...
  37. pmc To kill a tumor cell: the potential of proapoptotic receptor agonists
    Avi Ashkenazi
    Genentech, South San Francisco, California 94080, USA
    J Clin Invest 118:1979-90. 2008
    ..Novel molecular biomarkers may help identify those patients most likely to benefit from PARA therapy...
  38. pmc Antitherapeutic antibody-mediated hepatotoxicity of recombinant human Apo2L/TRAIL in the cynomolgus monkey
    Christina L Zuch de Zafra
    Safety Assessment, Genentech, Inc, 1 DNA Way, South San Francisco, CA 94080, USA
    Cell Death Dis 7:e2338. 2016
    ..The elucidation of this mechanism enabled successful transition of rhuApo2L/TRAIL into human clinical trials. ..
  39. doi request reprint Designer proteins to trigger cell death
    Wayne J Fairbrother
    Department of Early Discovery Biochemistry, Genentech, Inc, 1 DNA Way, South San Francisco, CA 94080, USA Electronic address
    Cell 157:1506-8. 2014
    ..use an innovative computational design approach coupled with in-vitro-targeted evolution to produce a potent polypeptide inhibitor of a viral Bcl-2-like protein. This novel inhibitor triggers apoptosis of virus-infected cells. ..
  40. doi request reprint E-cadherin couples death receptors to the cytoskeleton to regulate apoptosis
    Min Lu
    Cancer Immunology, Genentech, Inc, 1 DNA Way, South San Francisco, CA 94080, USA
    Mol Cell 54:987-98. 2014
    ..These results have potential implications for tissue homeostasis as well as cancer therapy...
  41. doi request reprint ImmunoPET imaging of phosphatidylserine in pro-apoptotic therapy treated tumor models
    Annie Ogasawara
    Genentech Research and Early Development gRED, Genentech Inc, 1 DNA Way, South San Francisco, CA 94080, USA
    Nucl Med Biol 40:15-22. 2013
    ....
  42. ncbi request reprint Selective knockdown of the long variant of cellular FLICE inhibitory protein augments death receptor-mediated caspase-8 activation and apoptosis
    Darcie A Sharp
    Department of Molecular Oncology, Genentech, Inc, South San Francisco, California 94080, USA
    J Biol Chem 280:19401-9. 2005
    ..Thus, endogenous c-FLIP(L) functions primarily as an inhibitor of death receptor-mediated apoptosis...
  43. pmc APRIL-deficient mice have normal immune system development
    Eugene Varfolomeev
    Department of Molecular Oncology, Genentech Inc, South San Francisco, California 94080, USA
    Mol Cell Biol 24:997-1006. 2004
    ..These data indicate that APRIL is dispensable in the mouse for proper development. Thus, BLyS may be capable of fulfilling APRIL's main functions...
  44. ncbi request reprint Design, construction, and in vitro analyses of multivalent antibodies
    Kathy Miller
    Department of Immunology, Genentech, Inc, South San Francisco, CA 94080, USA
    J Immunol 170:4854-61. 2003
    ....
  45. ncbi request reprint Tumor necrosis factor: an apoptosis JuNKie?
    Eugene E Varfolomeev
    Genentech, Inc, 1 DNA Way, South San Francisco, CA 94080, USA
    Cell 116:491-7. 2004
    ..Here, we review recent data on the role of JNK in the regulation of TNF-dependent apoptosis and discuss what is known so far about how cells decide whether to live or die in response to TNF...
  46. pmc Regulation of Apo2L/tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis in thyroid carcinoma cells
    Vassiliki Poulaki
    Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts 02114, USA
    Am J Pathol 161:643-54. 2002
    ..T helper-1 cytokines and compounds that selectively abrogate the IGF-1 signaling pathway may be helpful adjunct agents in Apo2L/TRAIL-based anti-cancer therapeutic regimens...
  47. ncbi request reprint Apo2L/TRAIL: apoptosis signaling, biology, and potential for cancer therapy
    Alexandru Almasan
    Department of Cancer Biology, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, OH 44195, USA
    Cytokine Growth Factor Rev 14:337-48. 2003
    ..In this review, we focus on the apoptosis signaling pathways stimulated by Apo2L/TRAIL, summarize what is known to date about the physiological role of this ligand and the potential for its application to cancer therapy...
  48. ncbi request reprint Elimination of hepatic metastases of colon cancer cells via p53-independent cross-talk between irinotecan and Apo2 ligand/TRAIL
    Rajani Ravi
    The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    Cancer Res 64:9105-14. 2004
    ....
  49. ncbi request reprint Toward small-molecule agonists of TNF receptors
    Sarah G Hymowitz
    Nat Chem Biol 1:353-4. 2005
  50. ncbi request reprint TNF-related apoptosis-inducing ligand (TRAIL)/Apo2L suppresses experimental autoimmune encephalomyelitis in mice
    Erika Cretney
    Cancer Immunology Program, Sir Donald and Lady Trescowthick Laboratories, Peter MacCallum Cancer Centre, Victoria, Australia
    Immunol Cell Biol 83:511-9. 2005
    ..These data are the first to illustrate the potential therapeutic value of recombinant TRAIL/Apo2L in suppressing T-cell-mediated autoimmune diseases...