Peter Zage

Title(s)Associate Professor In Residence, Pediatrics
SchoolHealth Sciences
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    Collapse Biography 
    Collapse Education and Training
    Children's Memorial Hospital, Chicago, IL2005Pediatric Hematology/Oncology
    University of Chicago Children's Hospital, Chicago, IL2002Pediatrics
    The Johns Hopkins University, Baltimore, MDBA1990Biology
    Columbia University College of Physicians & Surgeons, New York, NYMD, PhD1999Cell Biology

    Collapse Overview 
    Collapse Overview
    There is a critical need for new treatment options for children with relapsed and refractory solid tumors, and therapies directed against biologically relevant pathways are likely to be more effective with less toxicity. The goals of my clinical and translational research are to develop novel treatments and identify novel targets for therapies for children with solid tumors, in order to improve outcomes and to reduce the incidence and severity of the long-term side effects of current therapy. My primary laboratory projects include studies to better understand the pathways involved in the regulation of growth factor receptor trafficking and degradation in tumor cells and their role in tumor growth and treatment response in addition to studies to identify novel therapeutic targets and novel agents synergistic with established therapies.
    We have identified several promising novel targeted agents that are effective against pediatric solid tumors, and we have translated many of these therapies into early phase clinical trials for children with relapsed and refractory solid tumors. We have also identified a number of pathways required for neuroblastoma tumor cell survival, and these studies are likely to identify treatment combinations using readily available drugs that can also be rapidly tested in clinical trials, leading to improved treatments, reduced relapse rates, and improved survival for children with all forms of cancer.
    Our continued research looks to build on these findings through a better understanding of growth factor receptor trafficking and its link to chemotherapy responses and resistance to targeted therapies and through direct targeting of receptor trafficking as a unique approach to pediatric solid tumor therapy.

    Collapse Research 
    Collapse Research Activities and Funding
    The Role of Growth Factor Receptor Trafficking in Tumorigenesis
    NIH/NCI R01CA166749Apr 5, 2013 - Mar 31, 2018
    Role: Principal Investigator

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    Collapse Clinical Trials
    Collapse Featured Publications
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    Collapse Bibliographic 
    Collapse Publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Researchers can login to make corrections and additions, or contact us for help.
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    1. Zage PE. Novel Therapies for Relapsed and Refractory Neuroblastoma. Children (Basel). 2018 Oct 31; 5(11). PMID: 30384486.
      View in: PubMed
    2. Sholler GLS, Ferguson W, Bergendahl G, Bond JP, Neville K, Eslin D, Brown V, Roberts W, Wada RK, Oesterheld J, Mitchell D, Foley J, Parikh NS, Eshun F, Zage P, Rawwas J, Sencer S, Pankiewicz D, Quinn M, Rich M, Junewick J, Kraveka JM. Maintenance DFMO Increases Survival in High Risk Neuroblastoma. Sci Rep. 2018 Sep 27; 8(1):14445. PMID: 30262852.
      View in: PubMed
    3. Whittle SB, Smith V, Doherty E, Zhao S, McCarty S, Zage PE. Overview and recent advances in the treatment of neuroblastoma. Expert Rev Anticancer Ther. 2017 Apr; 17(4):369-386. PMID: 28142287.
      View in: PubMed
    4. Whittle SB, Patel K, Zhang L, Woodfield SE, Du M, Smith V, Zage PE. The novel kinase inhibitor ponatinib is an effective anti-angiogenic agent against neuroblastoma. Invest New Drugs. 2016 12; 34(6):685-692. PMID: 27586230.
      View in: PubMed
    5. Zage PE, Whittle SB, Shohet JM. CD114: A New Member of the Neural Crest-Derived Cancer Stem Cell Marker Family. J Cell Biochem. 2017 02; 118(2):221-231. PMID: 27428599.
      View in: PubMed
    6. Du M, Zhang L, Scorsone KA, Woodfield SE, Zage PE. Nifurtimox Is Effective Against Neural Tumor Cells and Is Synergistic with Buthionine Sulfoximine. Sci Rep. 2016 06 10; 6:27458. PMID: 27282514.
      View in: PubMed
    7. Whittle SB, Reyes S, Du M, Gireud M, Zhang L, Woodfield SE, Ittmann M, Scheurer ME, Bean AJ, Zage PE. A Polymorphism in the FGFR4 Gene Is Associated With Risk of Neuroblastoma and Altered Receptor Degradation. J Pediatr Hematol Oncol. 2016 Mar; 38(2):131-8. PMID: 26840079; PMCID: PMC4758892 [Available on 03/01/17].
    8. Woodfield SE, Zhang L, Scorsone KA, Liu Y, Zage PE. Binimetinib inhibits MEK and is effective against neuroblastoma tumor cells with low NF1 expression. BMC Cancer. 2016 Mar 01; 16:172. PMID: 26925841; PMCID: PMC4772351.
    9. Woodfield SE, Guo RJ, Liu Y, Major AM, Hollingsworth EF, Indiviglio S, Whittle SB, Mo Q, Bean AJ, Ittmann M, Lopez-Terrada D, Zage PE. Neuroblastoma patient outcomes, tumor differentiation, and ERK activation are correlated with expression levels of the ubiquitin ligase UBE4B. Genes Cancer. 2016 Jan; 7(1-2):13-26. PMID: 27014418.
      View in: PubMed
    10. Zhang L, Scorsone K, Woodfield SE, Zage PE. Sensitivity of neuroblastoma to the novel kinase inhibitor cabozantinib is mediated by ERK inhibition. Cancer Chemother Pharmacol. 2015 Nov; 76(5):977-87. PMID: 26407819.
      View in: PubMed
    11. Zhang L, Agarwal S, Shohet JM, Zage PE. CD114 Expression Mediates Melanoma Tumor Cell Growth and Treatment Resistance. Anticancer Res. 2015 Jul; 35(7):3787-92. PMID: 26124323.
      View in: PubMed
    12. Zhang H, Dou J, Yu Y, Zhao Y, Fan Y, Cheng J, Xu X, Liu W, Guan S, Chen Z, shi Y, Patel R, Vasudevan SA, Zage PE, Zhang H, Nuchtern JG, Kim ES, Fu S, Yang J. mTOR ATP-competitive inhibitor INK128 inhibits neuroblastoma growth via blocking mTORC signaling. Apoptosis. 2015 Jan; 20(1):50-62. PMID: 25425103.
      View in: PubMed
    13. Scorsone K, Zhang L, Woodfield SE, Hicks J, Zage PE. The novel kinase inhibitor EMD1214063 is effective against neuroblastoma. Invest New Drugs. 2014 Oct; 32(5):815-24. PMID: 24832869.
      View in: PubMed
    14. Brown BS, Patanam T, Mobli K, Celia C, Zage PE, Bean AJ, Tasciotti E. Etoposide-loaded immunoliposomes as active targeting agents for GD2-positive malignancies. Cancer Biol Ther. 2014 Jul; 15(7):851-61. PMID: 24755919.
      View in: PubMed
    15. Aguilar S, Louis C, Hicks J, Zage P, Russell H. Congenital neuroblastoma in a neonate with isotretinoin embryopathy. J Pediatr Hematol Oncol. 2014 Mar; 36(2):e75-7. PMID: 23652876.
      View in: PubMed
    16. Stricker TP, Morales La Madrid A, Chlenski A, Guerrero L, Salwen HR, Gosiengfiao Y, Perlman EJ, Furman W, Bahrami A, Shohet JM, Zage PE, Hicks MJ, Shimada H, Suganuma R, Park JR, So S, London WB, Pytel P, Maclean KH, Cohn SL. Validation of a prognostic multi-gene signature in high-risk neuroblastoma using the high throughput digital NanoString nCounter™ system. Mol Oncol. 2014 May; 8(3):669-78. PMID: 24560446; PMCID: PMC4004665.
    17. Sirisaengtaksin N, Gireud M, Yan Q, Kubota Y, Meza D, Waymire JC, Zage PE, Bean AJ. UBE4B protein couples ubiquitination and sorting machineries to enable epidermal growth factor receptor (EGFR) degradation. J Biol Chem. 2014 Jan 31; 289(5):3026-39. PMID: 24344129; PMCID: PMC3908433.
    18. Zage PE, Sirisaengtaksin N, Liu Y, Gireud M, Brown BS, Palla S, Richards KN, Hughes DP, Bean AJ. UBE4B levels are correlated with clinical outcomes in neuroblastoma patients and with altered neuroblastoma cell proliferation and sensitivity to epidermal growth factor receptor inhibitors. Cancer. 2013 Feb 15; 119(4):915-23. PMID: 22990745; PMCID: PMC3527637.
    19. Zage PE, Louis CU, Cohn SL. New aspects of neuroblastoma treatment: ASPHO 2011 symposium review. Pediatr Blood Cancer. 2012 Jul 01; 58(7):1099-105. PMID: 22378620; PMCID: PMC4104176.
    20. Wolff JE, Rytting ME, Vats TS, Zage PE, Ater JL, Woo S, Kuttesch J, Ketonen L, Mahajan A. Treatment of recurrent diffuse intrinsic pontine glioma: the MD Anderson Cancer Center experience. J Neurooncol. 2012 Jan; 106(2):391-7. PMID: 21858608; PMCID: PMC3990187.
    21. Zage PE, Nolo R, Fang W, Stewart J, Garcia-Manero G, Zweidler-McKay PA. Notch pathway activation induces neuroblastoma tumor cell growth arrest. Pediatr Blood Cancer. 2012 May; 58(5):682-9. PMID: 21744479; PMCID: PMC3264695.
    22. Singh A, Rokes C, Gireud M, Fletcher S, Baumgartner J, Fuller G, Stewart J, Zage P, Gopalakrishnan V. Retinoic acid induces REST degradation and neuronal differentiation by modulating the expression of SCF(ß-TRCP) in neuroblastoma cells. Cancer. 2011 Nov 15; 117(22):5189-202. PMID: 21523764.
      View in: PubMed
    23. Stephen MD, Zage PE, Waguespack SG. Gonadotropin-dependent precocious puberty: neoplastic causes and endocrine considerations. Int J Pediatr Endocrinol. 2011; 2011:184502. PMID: 21603196; PMCID: PMC3212801.
    24. Zage PE, Graham TC, Zeng L, Fang W, Pien C, Thress K, Omer C, Brown JL, Zweidler-McKay PA. The selective Trk inhibitor AZ623 inhibits brain-derived neurotrophic factor-mediated neuroblastoma cell proliferation and signaling and is synergistic with topotecan. Cancer. 2011 Mar 15; 117(6):1321-91. PMID: 20960503.
      View in: PubMed
    25. Levy AG, Zage PE, Akers LJ, Ghisoli ML, Chen Z, Fang W, Kannan S, Graham T, Zeng L, Franklin AR, Huang P, Zweidler-McKay PA. The combination of the novel glycolysis inhibitor 3-BrOP and rapamycin is effective against neuroblastoma. Invest New Drugs. 2012 Feb; 30(1):191-9. PMID: 20890785; PMCID: PMC4831635.
    26. Das CM, Zage PE, Taylor P, Aguilera D, Wolff JE, Lee D, Gopalakrishnan V. Chromatin remodelling at the topoisomerase II-beta promoter is associated with enhanced sensitivity to etoposide in human neuroblastoma cell lines. Eur J Cancer. 2010 Oct; 46(15):2771-80. PMID: 20886683.
      View in: PubMed
    27. Richards KN, Zweidler-McKay PA, Van Roy N, Speleman F, Trevino J, Zage PE, Hughes DP. Signaling of ERBB receptor tyrosine kinases promotes neuroblastoma growth in vitro and in vivo. Cancer. 2010 Jul 01; 116(13):3233-43. PMID: 20564646; PMCID: PMC2923448.
    28. Zage PE, Zeng L, Palla S, Fang W, Nilsson MB, Heymach JV, Zweidler-McKay PA. A novel therapeutic combination for neuroblastoma: the vascular endothelial growth factor receptor/epidermal growth factor receptor/rearranged during transfection inhibitor vandetanib with 13-cis-retinoic acid. Cancer. 2010 May 15; 116(10):2465-75. PMID: 20225331.
      View in: PubMed
    29. Nilsson MB, Zage PE, Zeng L, Xu L, Cascone T, Wu HK, Saigal B, Zweidler-McKay PA, Heymach JV. Multiple receptor tyrosine kinases regulate HIF-1alpha and HIF-2alpha in normoxia and hypoxia in neuroblastoma: implications for antiangiogenic mechanisms of multikinase inhibitors. Oncogene. 2010 May 20; 29(20):2938-49. PMID: 20208561.
      View in: PubMed
    30. Thress K, Macintyre T, Wang H, Whitston D, Liu ZY, Hoffmann E, Wang T, Brown JL, Webster K, Omer C, Zage PE, Zeng L, Zweidler-McKay PA. Identification and preclinical characterization of AZ-23, a novel, selective, and orally bioavailable inhibitor of the Trk kinase pathway. Mol Cancer Ther. 2009 Jul; 8(7):1818-27. PMID: 19509272.
      View in: PubMed
    31. Zage PE, Kletzel M, Murray K, Marcus R, Castleberry R, Zhang Y, London WB, Kretschmar C. Outcomes of the POG 9340/9341/9342 trials for children with high-risk neuroblastoma: a report from the Children's Oncology Group. Pediatr Blood Cancer. 2008 Dec; 51(6):747-53. PMID: 18704922; PMCID: PMC4426094.
    32. Zage PE, Reitman AJ, Seshadri R, Weinstein JL, Mets MB, Zeid JL, Greenwald MJ, Strauss LC, Goldman S. Outcomes of a two-drug chemotherapy regimen for intraocular retinoblastoma. Pediatr Blood Cancer. 2008 Mar; 50(3):567-72. PMID: 17729249.
      View in: PubMed
    33. Zhang M, Aguilera D, Das C, Vasquez H, Zage P, Gopalakrishnan V, Wolff J. Measuring cytotoxicity: a new perspective on LC50. Anticancer Res. 2007 Jan-Feb; 27(1A):35-8. PMID: 17352213.
      View in: PubMed
    34. Zhang M, Das C, Vasquez H, Aguilera D, Zage PE, Gopalakrishnan V, Wolff JE. Predicting tumor cell repopulation after response: mathematical modeling of cancer cell growth. Anticancer Res. 2006 Jul-Aug; 26(4B):2933-6. PMID: 16886616.
      View in: PubMed
    35. Chlenski A, Liu S, Guerrero LJ, Yang Q, Tian Y, Salwen HR, Zage P, Cohn SL. SPARC expression is associated with impaired tumor growth, inhibited angiogenesis and changes in the extracellular matrix. Int J Cancer. 2006 Jan 15; 118(2):310-6. PMID: 16052522.
      View in: PubMed
    36. Liu S, Tian Y, Chlenski A, Yang Q, Zage P, Salwen HR, Crawford SE, Cohn SL. Cross-talk between Schwann cells and neuroblasts influences the biology of neuroblastoma xenografts. Am J Pathol. 2005 Mar; 166(3):891-900. PMID: 15743800; PMCID: PMC1602341.
    37. Yang Q, Zage P, Kagan D, Tian Y, Seshadri R, Salwen HR, Liu S, Chlenski A, Cohn SL. Association of epigenetic inactivation of RASSF1A with poor outcome in human neuroblastoma. Clin Cancer Res. 2004 Dec 15; 10(24):8493-500. PMID: 15623630.
      View in: PubMed
    38. David FS, Zage PE, Marcantonio EE. Integrins interact with focal adhesions through multiple distinct pathways. J Cell Physiol. 1999 Oct; 181(1):74-82. PMID: 10457355.
      View in: PubMed
    39. Zage PE, Marcantonio EE. The membrane proximal region of the integrin beta cytoplasmic domain can mediate oligomerization. Cell Adhes Commun. 1998 Jul; 5(5):335-47. PMID: 9789682.
      View in: PubMed