Yousef Zakharia

Yousef Zakharia, MD is a medical oncologist specializing in genitourinary malignancies and early-phase experimental therapeutics at Mayo Clinic in Phoenix, Arizona. He currently serves as Chair of the Genitourinary Malignancy Disease Group within the Mayo Clinic Enterprise Comprehensive Cancer Center and as Medical Director of the Section of Experimental Therapeutics at Mayo Clinic Arizona. With more than 50 clinical trials as principal investigator and publications in journals including The New England Journal of Medicine, Journal of Clinical Oncology, Nature Communications, and Clinical Cancer Research, Yousef Zakharia is recognized as a leading figure in genitourinary oncology and translational research.

Current Positions

• Medical Oncologist, Mayo Clinic Arizona, Phoenix, Arizona (September 2024 – Present)
• Chair, Genitourinary Malignancy Disease Group, Mayo Clinic Comprehensive Cancer Center (2025 – Present)
• Medical Director, Section of Experimental Therapeutics, Mayo Clinic Arizona (2024 – Present)
• Leader, Kidney Cancer Program, Mayo Clinic Comprehensive Cancer Center (Present)
• Leader, Experimental Therapeutics and Phase I Clinics, Mayo Clinic (2024 – Present)

Education & Training

• M.D., Damascus University School of Medicine (2005)
• Residency, Diagnostic Radiology, Damascus University (2007)
• Residency, Internal Medicine, University of Rochester/Unity Hospital (2011)
• Fellowship, Hematology and Oncology, Michigan State University (2012)
• Fellowship, Hematology/Oncology, Georgia Regents University (2014)

Professional Experience

• Professor of Medicine, University of Iowa (2024; rank achieved prior to departure)
• Faculty, University of Iowa, Department of Medicine and Holden Comprehensive Cancer Center (2014–2024) — ten years of academic oncology faculty service
• Phase 1 Program Director, Holden Comprehensive Cancer Center, University of Iowa (2014–2024)
• Vice Chair, Genitourinary Malignancy Disease Group, Mayo Clinic Comprehensive Cancer Center (2024–2025)
• Co-Chair, Big Ten Genitourinary Clinical Trial Working Group (2022–2024)
• Co-Chair, ORIEN Clinical Trials Network (dates active per institutional record)
• Co-Chair, Immunotherapy Clinical Trial Working Group, Big Ten Cancer Consortium (2017–2019)
• Board Member, Board of Directors, Midwest Melanoma Partnership (2016–2020)
• Member, Institutional Review Board, University of Iowa (2019–2024)
• Member, Faculty Senate Governmental Relations Committee, University of Iowa (2021–2024)
• Member, Protocol Review and Monitoring Committee, University of Iowa Holden Comprehensive Cancer Center (2014–2020)
• Member, Protocol Review and Monitoring Committee, Georgia Regents University (2013–2014)

Research Activity

Yousef Zakharia’s research focuses on genitourinary oncology and the development of novel immunotherapy and targeted therapy approaches for kidney cancer, bladder cancer, prostate cancer, and melanoma. He has served as principal investigator on more than 50 clinical trials spanning investigator-initiated studies, industry-sponsored trials, and cooperative group studies. Key research areas include:

• Immunotherapy combinations in renal cell carcinoma, including epigenetic modulation with guadecitabine and PD-1/PD-L1 checkpoint inhibition
• Phase I/II trials of novel agents in advanced urothelial and bladder cancers, including antibody-drug conjugates, enfortumab vedotin-based regimens, and intravesical therapies
• Cabozantinib and pembrolizumab combinations in advanced cutaneous melanoma
• Telomerase vaccination combined with pembrolizumab in advanced melanoma
• Seleno-L-methionine in combination with axitinib in metastatic clear cell renal cell carcinoma
• Genomic and biomarker analyses of treatment response in urothelial carcinoma and prostate cancer
• Tumor microbiome as a predictor of immunotherapy outcomes
• Germline and somatic genomic sequencing in urinary tract cancers
• Outcomes research through multi-institutional collaborative databases including UNITE and REFINE
• Participation in landmark randomized controlled trials including the NIAGARA trial (perioperative durvalumab in bladder cancer, published in NEJM) and
• KEYNOTE-564 (adjuvant pembrolizumab in renal cell carcinoma, published in NEJM)

Certifications

• Medical Oncology, American Board of Internal Medicine (2014)
• Internal Medicine, American Board of Internal Medicine (2011)

Memberships

• Chair, Genitourinary Malignancy Disease Group, Mayo Clinic Comprehensive Cancer Center (2025 – Present)
• Member, Society for Immunotherapy of Cancer (SITC) (2017 – Present)
• Member, American Society of Clinical Oncology (ASCO) (2011 – Present)
• Member, American Society of Hematology (ASH)
• Member, American College of Physicians (ACP) (2008 – Present)
• Member, Syrian American Medical Society (SAMS) (2007 – Present)
• Member, Syrian Syndicate of Medicine (2005 – Present)

Areas of Specialization

• Genitourinary malignancies: kidney cancer, bladder cancer, prostate cancer, testicular cancer, penile cancer
• Renal cell carcinoma: immunotherapy combinations, targeted therapy, and clinical trial development
• Urothelial carcinoma: antibody-drug conjugates, enfortumab vedotin, checkpoint inhibitors, intravesical therapies
• Melanoma: immunotherapy and vaccine-based approaches
• Early-phase experimental therapeutics and Phase I clinical trials
• Translational and biomarker-driven oncology research
• Tumor microbiome and immune profiling
• Genomic characterization of genitourinary cancers

Publications

Yousef Zakharia has authored and co-authored more than 150 peer-reviewed publications in leading oncology journals including The New England Journal of Medicine, Journal of Clinical Oncology, Nature Communications, Cancer Discovery, Journal for ImmunoTherapy of Cancer, and Clinical Cancer Research. He has presented his work at major national and international meetings, including a plenary session at the American Association for Cancer Research (AACR) Annual Meeting in 2017.

Select Publications

Abou Chakra M, Alsamarah I, Hougen HY, Zakharia Y, et al. Computed tomography-derived extracellular volume fraction is associated with high-grade recurrence in non-muscle-invasive bladder cancer treated with intravesical gemcitabine and docetaxel. BJU Int. 2026 May 28. doi: 10.1111/bju.70319.
Maiocco G, Ernani V, Gustafson MP, Zakharia Y, et al. Cellular Therapies in Solid Tumors: Are We Ready for Primetime? JCO Oncol Pract. 2026 May 20. doi: 10.1200/OP-26-00119.
Kim D, Ged Y, Grivas P, Zakharia Y, et al. Association Between Proto-Oncogene N-RAS Transcript Level and Overall Survival in Node-Negative Muscle-Invasive Bladder Cancer. Clin Genitourin Cancer. 2026 Jun;24(4):102557.
Grier AL, Zhong JY, Basourakos S, Zakharia Y, et al. Recent Advances in Immunotherapy for Non-Muscle-Invasive Bladder Cancer. Cancers (Basel). 2026 Feb 14;18(4):623.
Zakharia Y, Kim D, Freesmeier M, et al. A phase 1b/2 study of cabozantinib in combination with pembrolizumab in advanced cutaneous melanoma. Cancer. 2026 Feb 15;132(4):e70326.
Jang A, Jindal T, Khaki AR, Zakharia Y, et al. Real-World Outcomes of Patients With Baseline Neuropathy and/or Diabetes Mellitus Receiving Enfortumab Vedotin-Based Regimens for Advanced Urothelial Carcinoma in the UNITE Database. Clin Genitourin Cancer. 2026 Mar;24(2):102501.
Jang A, Zakharia Y, Barata PC. Consensus and controversy in advanced urologic cancers: Insights from the Advanced Urologic Cancer Consensus Conference (AUC3) 2025. CA Cancer J Clin. 2026 Jan-Feb;76(1):e70056.
Kilari D, Henderson NC, Yamamoto K, Zakharia Y, et al. Impact of SPOP Mutations on Clinical Outcomes in Metastatic Prostate Cancer. JCO Precis Oncol. 2025 Dec;9:e2500590.
Jain P, Naqvi SAA, Tripathi N, Zakharia Y, et al. Real-World Outcomes of Enfortumab Vedotin and Pembrolizumab in Advanced Urothelial Carcinoma: A Multicenter Retrospective Analysis. Clin Genitourin Cancer. 2025 Dec;23(6):102453.
Raj P, Liu J, Zhu C, Zakharia Y, et al. Genetic haplotypes in VWA8, OSBPL6, and ADAMTS9-AS2 are associated with immune-related adverse effects in ICI-treated patients with cancer. J Immunother Cancer. 2025 Oct 28;13(10):e012012.
Jin N, Hoyd R, Yilmaz AS, Zakharia Y, et al. Epigenetic Modulation, Intratumoral Microbiome, and Immunity in Early-Onset Colorectal Cancer. Cancer Res Commun. 2025 Nov 1;5(11):1985–1997.
Panian J, Henderson NC, Herchenhorn D, Zakharia Y, et al. Genomic alterations and associated outcomes in patients with PSMA-positive metastatic castration-resistant prostate cancer treated with 177Lu-PSMA-617. Oncologist. 2025 Nov 11;30(11):oyaf358.
Jiang CY, Hwang H, Epstein IY, Zakharia Y, et al. Efficacy of erdafitinib before or after enfortumab vedotin in FGFR3-altered advanced urothelial cancer: analysis of the UNITE collaborative study. Oncologist. 2025 Nov 11;30(11):oyaf342.
Nizam A, Nguyen CB, Li J, Zakharia Y, et al. Treatment-Related Adverse Events and Associated Outcomes in Patients With Advanced Urothelial Carcinoma Treated With Enfortumab Vedotin: Analysis of the UNITE Study. Cancer Med. 2025 Oct;14(19):e71284.
Feng BJ, Kohlmann W, Nix DA, Zakharia Y, et al. Germline whole-exome sequencing reveals FOXP3-related gene variants conferring urinary cancer susceptibility and associated with immune escape. J Immunother Cancer. 2025 Sep 16;13(9):e010417.
Jindal T, Jiang CY, Alhalabi O, Zakharia Y, et al. Outcomes with Enfortumab Vedotin in Patients with Histologic Subtypes of Advanced Urothelial Carcinoma: Analysis of the UNITE Study. Eur Urol. 2025 Sep 14:S0302-2838(25)00490-7.
Shapiro DD, Abel EJ, Albiges L, Zakharia Y, et al. Developing biomarkers and methods of risk stratification: Consensus statements from the International Kidney Cancer Symposium North America 2024 Think Tank. Urol Oncol. 2025 Nov;43(11):639–653.
Milhem MM, Zakharia Y, Davar D, et al. Intratumoral vidutolimod as monotherapy or in combination with pembrolizumab in patients with programmed cell death 1 blockade-resistant melanoma: Final analysis from a phase 1b study. Cancer. 2025 Aug 1;131(15):e70022.
Wong MK, Milhem MM, Sacco JJ, Zakharia Y, et al. RP1 Combined With Nivolumab in Advanced Anti-PD-1-Failed Melanoma (IGNYTE). J Clin Oncol. 2025 Nov 20;43(33):3589–3599.
Menzies AM, Salman P, Frontera OA, Zakharia Y, et al. Administration of nivolumab plus ipilimumab: Infusion of the fixed-ratio combination versus sequential infusions in two randomized controlled trials of metastatic melanoma (CheckMate 742) and renal cell carcinoma (CheckMate 800). Cancer. 2025 Jul 15;131(14):e35962.
Zhong J, Jang A, Abuqayas B, Zakharia Y, et al. REFINE: a database of linked clinical data and genomic biomarkers in renal cell carcinoma patients receiving immunotherapy-based treatment regimens. Oncologist. 2025 Jun 4;30(6):oyaf135.
Garje R, Ravindra A, Rahim B, Zakharia Y, et al. Avelumab and taxol chemotherapy in platinum-refractory or ineligible metastatic urothelial carcinoma (AVETAX trial). Urol Oncol. 2025 Sep;43(9):520.e9–520.e18.
Bakaloudi DR, Talukder R, Enright T, Zakharia Y, et al. Response and Survival With Immune Checkpoint Inhibitor in Patients With Advanced Urothelial Carcinoma and Histology Subtypes. Clin Genitourin Cancer. 2025 Aug;23(4):102356.
Koch RM, Muniz M, Peskey CS, Zakharia Y, et al. Olanzapine for Managing Side Effects From Antiangiogenic Tyrosine-Kinase Inhibitors. J Pain Symptom Manage. 2025 Aug;70(2):182–188.
Zakharia Y, Reis RJ, Kroll MR, et al. Phase I Clinical Trial of High Doses of Seleno-L-methionine in Combination with Axitinib in Patients with Previously Treated Metastatic Clear-cell Renal Cell Carcinoma. Clin Cancer Res. 2025 Apr 1;31(7):1204–1211.
Masur J, Ratan A, Wierbilowicz K, Zakharia Y, et al. Clinical and Genomic Features of Androgen Indifferent Prostate Cancer. Int J Mol Sci. 2025 Jan 15;26(2):679.
Rataan AO, Xu Y, Geary SM, Zakharia Y, et al. Targeting transforming growth factor-β1 by methylseleninic acid/seleno-L-methionine in clear cell renal cell carcinoma: Mechanisms and therapeutic potential. Cancer Treat Res Commun. 2024;42:100864.
Talukder R, Bakaloudi DR, Makrakis D, Zakharia Y, et al. Clinical Outcomes With Immune Checkpoint Inhibitors in Patients With FGFR2/3, MTAP or ERBB2 Genomic Alterations in Advanced Urothelial Carcinoma. Clin Genitourin Cancer. 2025 Feb;23(1):102284.
Lee SM, Hamid O, Jotte R, Zakharia Y, et al. Phase II Open-Label Trial of Brentuximab Vedotin with Pembrolizumab in PD-1-Pretreated Metastatic Non-Small Cell Lung Cancer and Metastatic Cutaneous Melanoma. Clin Cancer Res. 2025 Mar 3;31(5):848–859.
Jindal T, Jiang C, Alhalabi O, Zakharia Y, et al. Genomic Biomarkers Associated with Enfortumab Vedotin Outcomes for Patients with Advanced Urothelial Carcinoma: Analysis of UNITE Study Data. Eur Urol Oncol. 2025 Apr;8(2):258–262.
von Itzstein MS, Liu J, Mu-Mosley H, Zakharia Y, et al. Racial Differences in Systemic Immune Parameters in Individuals With Lung Cancer. JTO Clin Res Rep. 2025 Jan;6(1):100751.
Berg SA, La Rosa S, Zhang T, Zakharia Y, et al. Impact of postprogression therapies on overall survival: Recommendations from the 2023 kidney cancer association think tank meeting. Urol Oncol. 2025 Mar;43(3):135–146.
Finnerty MC, Leach FE 3rd, Zakharia Y, et al. Identification of blood lipid markers of docetaxel treatment in prostate cancer patients. Sci Rep. 2024 Sep 27;14(1):22069.
Powles T, Catto JWF, Galsky MD, Zakharia Y, et al. Perioperative Durvalumab with Neoadjuvant Chemotherapy in Operable Bladder Cancer (NIAGARA). N Engl J Med. 2024 Nov 14;391(19):1773–1786.
Bakaloudi DR, Talukder R, Makrakis D, Zakharia Y, et al. Association of Tumor Mutational Burden and Microsatellite Instability With Response and Outcomes in Patients With Urothelial Carcinoma Treated With Immune Checkpoint Inhibitor. Clin Genitourin Cancer. 2024 Dec;22(6):102198.
Jamshidi F, Lozano L, Tucker B, Zakharia Y, et al. Belzutifan in Individuals with von Hippel-Lindau Retinal Hemangioblastomas: Institutional Experience and Review of the Literature. Ocul Oncol Pathol. 2024 Sep;10(3):154–161.
McElree IM, Packiam VT, Steinberg RL, Zakharia Y, et al. Sequential Endoluminal Gemcitabine and Cabazitaxel with Intravenous Pembrolizumab as a Bladder-Preserving Strategy for Docetaxel-Unresponsive Non-Muscle Invasive Urothelial Carcinoma Following Transurethral Resection of Bladder Tumor. Cancers (Basel). 2024 Jul 17;16(14):2561.
Dravillas CE, Coleman SS 4th, Hoyd R, Zakharia Y, et al. The Tumor Microbiome as a Predictor of Outcomes in Patients with Metastatic Melanoma Treated with Immune Checkpoint Inhibitors. Cancer Res Commun. 2024 Aug 1;4(8):1978–1990.
Kohlmann W, Nix DA, Pauley K, Zakharia Y, et al. Inherited Germline Variants in Urinary Tract Cancer: A Multicenter Whole-Exome Sequencing Analysis and Correlation With Clinical Features and Tumor Genomics. JCO Precis Oncol. 2024 Jun;8:e2300697.
Benej M, Hoyd R, Kreamer M, Zakharia Y, et al. The Tumor Microbiome Reacts to Hypoxia and Can Influence Response to Radiation Treatment in Colorectal Cancer. Cancer Res Commun. 2024 Jul 1;4(7):1690–1701.
Eule CJ, Hu J, Hedges D, Zakharia Y, et al. Clinical and Genomic Features of Patients with Renal Cell Carcinoma and Advanced Chronic Kidney Disease: Analysis of a Multi-Institutional Database. Cancers (Basel). 2024 May 18;16(10):1920.
Choueiri TK, Tomczak P, Park SH, Zakharia Y (KEYNOTE-564 Investigators), et al. Overall Survival with Adjuvant Pembrolizumab in Renal-Cell Carcinoma. N Engl J Med. 2024 Apr 18;390(15):1359–1371.
Park JJ, Chu A, Li J, Zakharia Y, et al. Repeat Next-Generation Sequencing Testing on Progression in Men With Metastatic Prostate Cancer Can Identify New Actionable Alterations. JCO Precis Oncol. 2024 Apr;8:e2300567.
Zorko NA, Makovec A, Elliott A, Zakharia Y, et al. Natural Killer Cell Infiltration in Prostate Cancers Predict Improved Patient Outcomes. Prostate Cancer Prostatic Dis. 2025 Mar;28(1):129–137.
Zakharia Y, Singer EA, Acharyya S, et al. Durvalumab and guadecitabine in advanced clear cell renal cell carcinoma: results from the phase Ib/II study BTCRC-GU16-043. Nat Commun. 2024 Feb 1;15(1):972.
Gulati S, Hsu CY, Shah S, Zakharia Y, et al. Systemic Anticancer Therapy and Thromboembolic Outcomes in Hospitalized Patients With Cancer and COVID-19. JAMA Oncol. 2023 Oct 1;9(10):1390–1400.
Bakaloudi DR, Talukder R, Lin GI, Zakharia Y, et al. Response and Outcomes of Maintenance Avelumab After Platinum-Based Chemotherapy in Patients With Advanced Urothelial Carcinoma: “Real World” Experience. Clin Genitourin Cancer. 2023 Oct;21(5):584–593.
Alameddine R, Mallea P, Shahab F, Zakharia Y. Antibody Drug Conjugates in Bladder Cancer: Current Milestones and Future Perspectives. Curr Treat Options Oncol. 2023 Sep;24(9):1167–1182.
Ellingsen EB, O’Day S, Mezheyeuski A, Milhem M, Zakharia Y, et al. Clinical Activity of Combined Telomerase Vaccination and Pembrolizumab in Advanced Melanoma: Results from a Phase I Trial. Clin Cancer Res. 2023 Aug 15;29(16):3026–3036.
Duarte C, Hu J, Beuselinck B, Zakharia Y, et al. Metastatic renal cell carcinoma to the pancreas and other sites — a multicenter retrospective study. EClinicalMedicine. 2023 Jun 1;60:102018.
Mar N, Zakharia Y, Falcon A, et al. Results from a Phase 1b/2 Study of Ibrutinib Combination Therapy in Advanced Urothelial Carcinoma. Cancers (Basel). 2023 May 30;15(11):2978.

All information is sourced from publicly available materials