Research Interests:
Assessment of host and tumor contributions to efficacy and drug resistance following antiangiogenic and immune-checkpoint treatment Development of clinically relevant mouse models of advanced metastatic disease Discovery of biomarkers to aid in clinical optimization of VEGF and PD-1 pathway inhibitor useAbout John Ebos
Biography:
Dr. Ebos completed his undergraduate training at McGill University (B.Sc Biology; philosophy minor) and earned his Ph.D. in the Department of Medical Biophysics at the University of Toronto where he studied novel circulating molecules as potential surrogate markers of cancer progression and antiangiogenic drug efficacy.
Positions
Roswell Park Comprehensive Cancer Center
- Associate Professor of Oncology
- Department of Cancer Genetics and Genomics
- Department of Medicine
- Department of Pharmacology and Therapeutics (Graduate Program)
Background
Education and Training:
- PhD — Medical Biophysics, University of Toronto, Toronto, Canada
- BSc — Biology, McGill University, Montreal, Canada
Research
Research Overview:
Dr. Ebos’ laboratory currently focuses on the molecular mechanisms that drive intrinsic and acquired drug resistance to inhibitors of the tumor microenvironment and their impact on spontaneous metastatic disease. Of particular interest is the study of off-target ‘host’ effects following therapy that may alter disease progression and be exploited as biomarkers. The long-term goal of these efforts is pair novel experimental therapeutic testing in clinically relevant preclinical models with ongoing patient trials to more readily predict subsequent/alternative therapies to improve overall efficacy.
*Currently accepting MSc, PhD, and post-doctoral trainees
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Publications
Full Publications list on PubMed
- Dolan M, Mastri M, Tracz A, Attwood K, Christensen JG, Chatta G, Ebos JML (2019). “Enhanced efficacy of Sitravatinib in metastatic models of antiangiogenic therapy resistance”. Plos One 14(8):e022010
- Mastri M and Ebos JML (2019) “Tumor growth fueled by spurious senescence phenotypes”. Molecular and Cellular Oncology 6 (2), 1575707.
- Mastri M, Tracz A, Lee CR, Dolan M, Attwood K, Christensen JG, Liu S, Ebos JML (2018) “A transient pseudosenescent secretome promotes tumor growth following antiangiogenic therapy withdrawal”. Cell Reports 25, 3706–3720.
- Mastri M, Tracz A, Lee CR, Attwood K, Kerbel RS, Dolan M, Shi Y, Ebos JML (2018). “Tumor-independent host secretomes induced by angiogenesis and immune-checkpoint inhibitors”. Molecular Cancer Therapeutics 17(7):1602-1612.
- Dufies M, Giuliano S, Ambrosetti D, Claren A, Ndiaye PD, Mastri M, Moghrabi W, Cooley LS, Ettaiche M, Chamorey E, Parola J, Vial V, Lupu-Plesu M, Bernhard JC , Ravaud A, Borchiellini D, Ferrero JM, Bikfalvi A, Ebos JML, Khabar KS, Grepin R. (2017) “Sunitinib stimulates expression of VEGFC by tumor cells and promotes lymphangiogenesis in clear cell renal cell carcinomas” Cancer Research 77(5):1212-1226
- Torres-Estay V, Carreño DV, Fuenzalida P, Watts A, San Francisco IF, Montecinos VP, Sotomayor PC, Ebos JML, Smith GJ, Godoy AS. (2017) “Androgens modulate male-derived endothelial cell homeostasis using androgen receptor-dependent and receptor-independent mechanisms” Angiogenesis 20(1):25-38
- Ebos JML & Quintela-Fandino M (2016) “Revisiting the revolution: Examining the evolving role of antiangiogenic therapy in cancer” Current Drug Targets 17(15):1706.
- Mastri M, Rosario S, Tracz A, Frink RE, Brekken RA, Ebos JML (2016) “The challenges of modeling drug resistance to antiangiogenic therapy’. Current Drug Targets 17(15):1747-1754).
- Benzekry S, Tracz A, Mastri M, Corbelli R, Barbolosi D, Ebos JML (2016) “Modeling spontaneous metastasis following surgery: An in vivo/ in silico approach” Cancer Research 1;76(3):535-47
- Ebos JML (2015) “Prodding the Beast: Assessing the implications of treatment-induced metastasis” Cancer Research. 75(17):3427-3435
- Ebos JML, Mastri M, Lee CR, Tracz A, Hudson JM, Attwood K, Cruz-Munoz W, Jedeszko C, Burns P, Kerbel RS (2014) “Neoadjuvant antiangiogenic therapy reveals contrasts in primary and metastatic tumor efficacy” EMBO Molecular Medicine 6(12):1561-76
- Benzekry S, Lamont C, Beheshti A, Tracz A, Ebos JML, Hlatky L, Hahnfeldt P (2014) “Classical Mathematical Models for Description and Prediction of Experimental Tumor Growth”. PLOS Computational Biology 10(8): e1003800
- Mittal K, Ebos JML, Rini B. (2014) ‘Angiogenesis and the Tumor Microenvironment: VEGF and Beyond’. Seminars in Oncology. 41(2):235-51.
- Tracz, A., Mastri, M., Pili, R., Ebos JML (2014) “Modeling spontaneous metastatic renal cell carcinoma (mRCC) in mice following nephrectomy”. Journal of Visualized Experiments (86).
- Kerbel RS, Guerin E, Francia G, Xu P, Lee CR, Ebos JML, Man S. (2013) “Preclinical recapitulation of antiangiogenic drug clinical efficacies using models of early or late stage breast cancer metastasis”. Breast. Suppl. 2:S57-65
- Ebos JML & Pili R (2012) “Mind the Gap: Potential for Rebounds during Antiangiogenic Treatment Breaks” Clinical Cancer Research 18(14):3719-21.
- Ebos JML & Kerbel RS. (2011) “Disease Progression after Antiangiogenic Therapy: Implications for Invasion and Metastasis” Nature Reviews Clinical Oncology 8:210-221
- Kerbel RS & Ebos JML (2010) “An Inhospitable Host?”. Nature Medicine 16(10):1084-5.
- Mamluk R, Carvajal IM, Morse BA, Wong H, Abramowitz J, Aslanian S, Lim AC, Gokemeijer J, Storek MJ, Lee J, Gosselin M, Wright MC, Camphausen RT, Wang J, Chen Y, Miller K, Sanders K, Konerding MA, Ackermann M, Sperinde J, Prasad G, Williams S, Kerbel RS, Ebos JML, Mendlein JD, Harris AS, Furfine ES (2009) “Anti-tumor effect of CT-322 as an Adnectin inhibitor of vascular endothelial growth factor receptor-2”. mAbs Journal 2(2):199–208.
- Wong NS, Buckman RB, Clemons M, Verma S, Dent S, Trudeau ME, Roche K, Ebos JML, Kerbel RS, DeBoer GE, Sutherland DJA, Emmenegger U, Slingerland J, Gardner S, Pritchard KI. (2009) Phase I-II trial of metronomic chemotherapy with daily dalteparin and cyclophosphamide, twice weekly methotrexate and daily prednisone (DalCMP) as therapy for metastatic breast cancer using soluble vascular endothelial growth factor receptor levels as markers of response. Journal of Clinical Oncology 28(5):723-30
- Ebos JML, Lee CR, & Kerbel RS. (2009) “Tumor- and host-mediated pathways of resistance and disease progression in response to antiangiogenic therapy”. Clinical Cancer Research 15(16):5020-5.
- Mutsaers AJ, Francia G, Man S, Lee CR, Ebos JML, Wu Y, Witte L, Berry S, Moore M, Kerbel RS (2009) “Cetuximab causes a dose-dependent increase in circulating transforming growth factor-a that acts as pharmacodynamic marker for optimal biologic dosing and are tumor-independent”. Clinical Cancer Research 15(7):2397-405.
- Ebos JML, Lee CR, Cruz W, Bjarnason GA, Christensen JG, & Kerbel RS. (2009) “Acceleration of metastasis after short-term treatment with a potent inhibitor of angiogenesis”. Cancer Cell 15(3):232-9.
- Ebos JML, Lee CR, Bogdanovic E, Almani J, Van Slyke P, Francia F, Xu P, Mutsaers AJ, Dumont DJ, and Kerbel RS (2008) “VEGF-mediated decrease in plasma sVEGFR-2 levels as a Surrogate Biomarker for Tumor Growth”. Cancer Research. 68(2):521-9.
- Ebos JML, Lee CR, Christensen JG, Mutsaers AJ, and Kerbel RS. (2007) “Multiple Circulating Pro-Angiogenic Factors Systemically Induced by Sunitinib Malate (SU11248) are Tumor-Independent and Correlate with Anti-Tumor Efficacy”. Proceedings of the National Academy of Sciences 104(43):17069-74
- Shaked Y, Bocci G, Munoz R, Man S, Ebos JML, Hicklin DJ, Bertolini F, D’Amato R, Kerbel RS (2005) “Cellular and Molecular Surrogate Markers to Monitor Targeted and Non-Targeted Antiangiogenic Drug Activity and Determine Optimal Biologic Dose”. Current Cancer Drug Targets. 5:551-559
- Francia F, Green SK, Bocci G, Man S, Emmenegger U, Ebos JML, Weinerman A, Shaked Y, Kerbel RS (2005) “Downregulation of DNA mismatch repair proteins in human and murine tumor spheroids: implications for multicellular resistance to alkylating agents”. Molecular Cancer Therapeutics 4(10):1484-94.
- Bocci G, Man S, Green SK, Francia G, Ebos JML, du Manoir JM, Weinerman A, Emmenegger U, Ma L, Thorpe P, Davidoff A, Huber J, Hicklin DJ, Kerbel RS. (2004) “Increased Levels of Circulating Plasma VEGF as a Surrogate Marker for Optimal Biologic Dosing of Antiangiogenic VEGFR-2 Monoclonal Antibodies”. Cancer Research 64 (18):6616-25.
- Ebos JML, Bocci G, Man S, Thorpe PE, Hicklin DJ, Zhou D, Jia X, Kerbel RS. (2004) “A naturally occurring soluble form of vascular endothelial growth factor receptor 2 detected in mouse and human plasma”. Molecular Cancer Research. 2(6):315-26
- Master Z, Tran J, Bishnoi A, Ebos JML, VanSlyke P, Kerbel RS & Dumont DJ. (2003) “Dok-R binds c-Abl and regulates Abl kinase activity and mediates cytoskeletal reorganization”. Journal of Biological Chemistry. 278(32):30170-
- Ebos JML, Tran J, Master Z, Dumont D, Melo JV, Buchdunger E, & Kerbel RS. (2002) “Imatinib mesylate (STI 571) reduces Bcr-Abl mediated VEGF secretion in chronic myelogenous leukemia”. Molecular Cancer Research. 1(2):89-95