Jason Chesney, M.D., Ph.D.

Education:

B.A., Anthropology, Summa Cum Laude, University of Minnesota, 1987-1991
Ph.D., Biomedical Sciences, University of Minnesota Graduate School, 1993-1997
M.D., University of Minnesota Medical School, 1991-1998
Internship and Residency, Cornell University Medical College, 1998-2001
Residency, Memorial Sloan Kettering Cancer Center, 1998-2001
Board Certified, American Board of Internal Medicine, 2001-2011
Clinical Fellowship, Immunology, Cornell University Medical College, 2001-2002
Post-Graduate Clinical Training, Medical Oncology/Hematology, University of Louisville, 2003-2005

Curriculum Vitae

Current Positions:

Director, James Graham Brown Cancer Center, University of Louisville
James Graham Brown Foundation Endowed Chair, James Graham Brown Cancer Center
Professor, Depts. of Medicine (Hematology/Oncology), Biochemistry/Molecular Biology, and Pharmacology/Toxicology
Director, James Graham Brown Cancer Center Clinical Research Program and Biorepository
Chairman, Medical Oncology and Hematology Data and Safety Monitoring Committee

Contact Information:


502-852-3679

Clinical Focus and Research

Dr. Chesney's clinical focus is on multi-disciplinary approaches to the treatment of metastatic melanoma and multiple solid tumor types including lung, colon, breast and kidney cancers.  He works with with Donald Miller, M.D., Ph.D. (Medical Oncology), Kelly McMasters, M.D., Ph.D. (Surgical Oncology), and Craig Silverman, M.D., (Radiation Oncology) to ensure that their patients receive the most effective combination of treatment modalities and have access to the most innovative drugs for the treatment of melanoma and all types of cancer.

His group’s immunotherapeutic clinical trials program is focused on testing novel approaches to cause durable remissions through induction of tumor immunity in advanced solid malignancies. They were the first to demonstrate that denileukin diftitox, an FDA-approved agent for a rare sub-type of lymphoma, can deplete T regulatory cells that normally suppress immunity against cancers, causing objective clinical responses in stage IV melanoma patients (1).  Based on the success of the denileukin diftitox trial, Dr. Chesney became interested in blocking other immune checkpoints such as CTLA4 that prevent immune responses against cancers. He served as the institutional Principal Investigator on a randomized Phase II dose-ranging study of a novel anti-CTLA4 antibody (ipilimumab) (2) and a Phase I single arm study to establish the safety of administering another anti-CTLA4 antibody (tremelimumab) (3).  The positive results of these two sponsored trials has resulted in the development of several trials that rationally combine anti-CTLA4 antibodies with other immunotherapies including GM-CSF (clinicaltrials.gov NCT02009397), IL-21 (NCT01489059), denileukin diftitox (NCT02009384), the oncolytic virus, T-VEC  (NCT01740297, NCT02014441, NCT02211131, NCT02297529, NCT00769704) (4), and the anti-PD1, nivolumab (NCT01927419) (5). Importantly, the Dr. Chesney's clinical research team at the J. Graham Brown Cancer Center and his colleagues at Memorial Sloan Kettering Cancer Center were the top two accruing centers worldwide to find that the combination of two immune checkpoint inhibitors, ipilimumab and nivolumab, resulted in the highest objective response rate ever observed after treatment with an immunotherapy (5). Dr. Chesney's research laboratory also is focused on the pre-clinical development of novel experimental therapeutics and, working with Dr. John Trent and Advanced Cancer Therapeutics, they have discovered a drug called PFK158 that blocks cancer sugar metabolism and that is currently undergoing evaluation by Dr. Rebecca Redman in a phase I trial (Phase 1 Safety Study of ACT-PFK-158, 2HCl in Patients With Advanced Solid Malignancies, clinicaltrials.gov #NCT02044861).

Dr. Chesney is funded by the National Cancer Institute, the Congressionally Directed Medical Research Program and the National Center for Research Resources as well as multiple pharmaceutical sponsors.  He serves as a reviewer on multiple National Cancer Institute subcommittees to evaluate Specialized Programs of Research Excellence (SPOREs), Tumor Cell Biology and P30-Designated Cancer Center grants. He has been named a Top Doctor by U.S. News and World Report for Solid Tumors and Clinical Trials and is the recipient of the Kentucky Derby Julep Scientist of the Year Award.

Learn more about Dr. Chesney's basic research on cancer metabolism and experimental therapeutics.

Literature Cited:

  1. Ready N, Hellmann MD, Awad MM, Otterson GA, Gutierrez M, Gainor JF, Borghaei H, Jolivet J, Horn L, Mates M, Brahmer J, Rabinowitz I, Reddy PS, Chesney J, Orcutt J, Spigel DR, Reck M, O'Byrne KJ, Paz-Ares L, Hu W, Zerba K, Li X, Lestini B, Geese WJ, Szustakowski JD, Green G, Chang H, Ramalingam SS.  First-line Nivolumab plus Ipilimumab in advanced non-small-cell lung cancer (CheckMate 568): Outcomes by programmed death ligand 1 and tumor mutational burden as biomarkers.  Journal of Clinical Oncology 2019 Feb 20:JCO1801042. doi: 10.1200/JCO.18.01042. [Epub ahead of print] PMID: 30785829.
  2. Gill A, Gosain R, Gragg H, Bycroft R, Rai SN, Pan J, Chesney JA, Miller DM.  5-(3,3-dimethyle-1-triazeno) imidazole-4-carboxamide and interleukin-2 adjuvant therapy in resected high-risk primary and regionally metastatic melanoma.  American Journal of Medical Science 2019 Jan;357(1):43-48. doi: 10.1016/j.amjms.2018.10.009. Epub 2018 Oct 25. PMID: 30611319.
  3. Mondal S, Roy D, Sarkar Bhattacharya S, Jin L, Jung D, Zhang S, Kalogera E, Staub J, Wang Y, Xuyang W, Khurana A, Chien J, Telang S, Chesney J, Tapolsky G, Petras D, Shridhar V.  Therapeutic targeting of PFKFB3 with a novel glycolytic inhibitor PFK158 promotes lipophagy and chemosensitivity in gynecologic cancers.  International Journal of Cancer 2019 Jan 1;144(1):178-89. doi: 10.1002/ijc.31868. Epub 2018 Oct 30. PMID: 30226266; PMCID: PMC6261695.
  4. Rodig SJ, Gusenleitner D, Jackson DG, Gjini E, Giobbie-Hurder A, Jin C, Chang H, Lovitch SB, Horak C, Weber JS, Weirather JL, Wolchok JD, Postow MA, Pavlick AC, Chesney J, Hodi FS.  MHC proteins confer differential sensitivity to CTLA-4 and PD-1 blockade in untreated metastatic melanoma.  Science Translational Medicine 2018 Jul 18;10(450). pii: eaar3342. doi: 10.1126/scitranslmed.aar3342. PMID: 30021886.
  5. Velazquez-Campoy A, Vega S, Sanchez-Gracia O, Lanas A, Rodrigo A, Kaliappan A, Hall MB, Nguyen TQ, Brock GN, Chesney JA, Garbett NC, Abian O.  Thermal liquid biopsy for monitoring melanoma patients under surveillance during treatment: A pilot study.  Biochimica et Biophysica Acta General Subjects 2018 Aug;1862(8):1701-10. doi: 10.1016/j.bbagen.2018.04.020. Epub 2018 Apr 26. PMID: 29705200.
  6. Chesney J, Imbert-Fernandez Y, Telang S, Baum M, Ranjan S, Fraig M, Batty N.  Potential clinical and immunotherapeutic utility of talimogene laherparepvec for patients with melanoma after disease progression on immune checkpoint inhibitors and BRAF inhibitors.  Melanoma Research 2018 Jun;28(3):250-5. doi: 10.1097/CMR.0000000000000444. PMID: 29561296; PMCID: PMC5929488.
  7. Chesney J, Awasthi S, Curti B, Hutchins L, Linette G, Triozzi P, Tan MCB, Brown RE, Nemunaitis J, Whitman E, Windham C, Lutzky J, Downey GF, Batty N, Amatruda T.  Phase IIIb safety results from an expanded-access protocol of talimogene laherparepvec for patients with unresected, stage IIIB-IVM1c melanoma.  Melanoma Research 2018 Feb;28(1):44-51. doi: 10.1097/CMR.0000000000000399. PMID: 29176501.
  8. Chesney J, Puzanov I, Collichio F, Singh P, Milhem MM, Glaspy J, Hamid O, Ross M, Friedlander P, Garbe C, Logan TF, Hauschild A, Lebbé C, Chen L, Kim JJ, Gansert J, Andtbacka RHI, Kaufman HL.  Randomized, open-label phase II study evaluating the efficacy and safety of talimogene laherparepvec in combination with ipilimumab versus ipilimumab alone in patients with advanced, unresectable melanoma.  Journal of Clinical Oncology 2018 Jun 10;36(17):1658-67. doi: 10.1200/JCO.2017.73.7379. Epub 2017 Oct 5. PMID: 28981385; PMCID: PMC6075852.
  9. Schadendorf D, Wolchok JD, Hodi FS, Chiarion-Sileni V, Gonzalez R, Rutkowski P, Grob JJ, Cowey CL, Lao CD, Chesney J, Robert C, Grossmann K, McDermott D, Walker D, Bhore R, Larkin J, Postow MA.  Efficacy and safety outcomes in patients with advanced melanoma who discontinued treatment with Nivolumab and Ipilimumab because of adverse events: A pooled analysis of randomized phase II and III trials.  Journal of Clinical Oncology 2017 Dec 1;35(34):3807-14. doi: 10.1200/JCO.2017.73.2289. Epub 2017 Aug 25. PMID: 28841387; PMCID: PMC5791828.
  10. Chesney JA, Mitchell RA, Yaddanapudi K. Myeloid-derived suppressor cells-a new therapeutic target to overcome resistance to cancer immunotherapy.  Journal of Leukocyte Biology 2017 Sep;102(3):727-40. doi: 10.1189/jlb.5VMR1116-458RRR. Epub 2017 May 25. Review. PMID: 28546500.
  11. Yusuf MB, Amsbaugh MJ, Burton E, Chesney J, Woo S.  Peri-SRS administration of immune checkpoint therapy for melanoma metastatic to the brain: Investigating efficacy and the effects of relative treatment timing on lesion response.  World Neurosurgery 2017 Apr;100:632-640.e4. doi: 10.1016/j.wneu.2017.01.101. Epub 2017 Feb 4. PMID: 28179176.
  12. Yalcin A, Solakoglu TH, Ozcan SC, Guzel S, Peker S, Celikler S, Balaban BD, Sevinc E, Gurpinar Y, Chesney JA.  6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase-3 is required for transforming growth factor β1-enhanced invasion of Panc1 cells in vitroBiochemical & Biophysical Research Communications 2017 Mar 11;484(3):687-93. doi: 10.1016/j.bbrc.2017.01.178. Epub 2017 Feb 1. PMID: 28161638.
  13. Hodi FS, Chesney J, Pavlick AC, Robert C, Grossmann KF, McDermott DF, Linette GP, Meyer N, Giguere JK, Agarwala SS, Shaheen M, Ernstoff MS, Minor DR, Salama AK, Taylor MH, Ott PA, Horak C, Gagnier P, Jiang J, Wolchok JD, Postow MA.  Combined nivolumab and ipilimumab versus ipilimumab alone in patients with advanced melanoma: 2-year overall survival outcomes in a multicentre, randomised, controlled, phase 2 trial.  Lancet Oncology 2016 Nov;17(11):1558-68. doi: 10.1016/S1470-2045(16)30366-7. Epub 2016 Sep 9. PMID: 27622997; PMCID: PMC5630525.
  14. Andtbacka R, Kaufman H, Collichio F, Amatruda T, Senzer N, Chesney J, Delman KA, Spitler LE, Puzanov I, Agarwala SS, Milhem M, Cranmer L, Curti B, Lewis K, Ross M, Guthrie T, Linette GP, Daniels GA, Harrington K, Middleton MR, Miller WH, Zager JS, Ye Y, Yao B, Li A, Doleman S,  VanderWalde A, Gansert J, Coffin R.  Talimogene laherparepvec improves durable response rate in patients with advanced melanoma.  Journal of Clinical Oncology 2015 Sep 1;33(25):2780-8.  PMID:26014293
  15. Postow MA, Chesney J, Pavlick AC, Rober C, Grossmann K, McDermott D, Linette G, Meyer N, Giguere JK, Agarwala S, Shaheen M, Ernstoff MS, Minor D, Salama AK, Taylor M, Ott PA, Rollin LM, Horak C, Gagnier P, Wolchok J, Hodi FS.  Nivolumab and Ipilimumab versus Ipilimumab in untreated melanoma.  New England Journal of Medicine 2015 May 21;372(21):2006-17.  PMID:25891304; PMCID: PMC5744258.
  16. Schoors S, De Bock K, Cantelmo AR, Georgiadou M, Ghesquière B, Cauwenberghs S, Kuchnio A, Wong BW, Quaegebeur A, Goveia J, Bifari F, Wang X, Blanco R, Tembuyser B, Cornelissen I, Bouché A, Vinckier S, Diaz-Moralli S, Gerhardt H, Telang S, Cascante M, Chesney J, Dewerchin M, Carmeliet P.  Partial and transient reduction of glycolysis by PFKFB3 blockade reduces pathological angiogenesis.  Cell Metabolism 2014 Jan 7;19(1):37-48. doi: 10.1016/j.cmet.2013.11.008. Epub 2013 Dec 12. PMID: 24332967.
  17. Liu Y, Sánchez-Tilló E, Lu X, Clem B, Telang S, Jenson AB, Cuatrecasas M, Chesney J, Postigo A, Dean DC.  Rb1 family mutation is sufficient for sarcoma initiation.  Nature Communications 2013;4:2650. doi: 10.1038/ncomms3650. PMID: 24150016.
  18. De Bock K, Georgiadou M, Schoors S, Kuchnio A, Wong BW, Cantelmo AR, Quaegebeur A, Ghesquière B, Cauwenberghs S, Eelen G, Phng LK, Betz I, Tembuyser B, Brepoels K, Welti J, Geudens I, Segura I, Cruys B, Bifari F, Decimo I, Blanco R, Wyns S, Vangindertael J, Rocha S, Collins RT, Munck S, Daelemans D, Imamura H, Devlieger R, Rider M, Van Veldhoven PP, Schuit F, Bartrons R, Hofkens J, Fraisl P, Telang S, Deberardinis RJ, Schoonjans L, Vinckier S, Chesney J, Gerhardt H, Dewerchin M, Carmeliet P.  Role of PFKFB3-driven glycolysis in vessel sprouting.  Cell 2013 Aug 1;154(3):651-63. doi: 10.1016/j.cell.2013.06.037. PMID: 23911327.
  19. Clem BF, O'Neal J, Tapolsky G, Clem AL, Imbert-Fernandez Y, Kerr DA 2nd, Klarer AC, Redman R, Miller DM, Trent JO, Telang S, Chesney J.  Targeting 6-phosphofructo-2-kinase (PFKFB3) as a therapeutic strategy against cancer.  Molecular Cancer Therapeutics 2013 Aug;12(8):1461-70. doi: 10.1158/1535-7163.MCT-13-0097. Epub 2013 May 14. PMID: 23674815; PMCID: PMC3742633.
  20. Liu Y, Sánchez-Tilló E, Lu X, Huang L, Clem B, Telang S, Jenson AB, Cuatrecasas M, Chesney J, Postigo A, Dean DC.  Sequential inductions of the ZEB1 transcription factor caused by mutation of Rb and then Ras proteins are required for tumor initiation and progression.  Journal of Biological Chemistry 2013 Apr 19;288(16):11572-80.  doi: 10.1074/jbc.M112.434951. Epub 2013 Feb 26. PMID: 23443660; PMCID: PMC3630860.
  21. Ribas A, Chesney J, Gordon MS, Aberneth AP, Logan TF, Lawson DH, Chmielowksi B, Huang B, Wang E, Poe-Hirr H, Gomez-Navarro J, Gerhardt D, Marshall MA, Gonzalez RC.  Safety profile and pharmacokinetic analysis of the anti-CTLA4 antibody tremelimumab administered as a one hour infusion.  Journal of Translational Medicine 10(1):236, 2012.  PMID: 23171508.
  22. Kim KB, Chesney J, Robinson D, Gardner H, Shi MM, Kirkwood JM.  Phase I/II and pharmacodynamic study of dovitinib (TKI258), an inhibitor of fibroblast growth factor receptors and VEGF receptors, in patients with advanced melanoma.  Clinical Cancer Research 2011 Dec 1;17(23):7451-61. doi: 10.1158/1078-0432.CCR-11-1747. Epub 2011 Oct 5. PMID: 21976540.
  23. Chesney J, McMasters KM.  Immunotherapy: Tumor-infiltrating T cells--ready for  prime time in melanoma? Nature Reviews Clinical Oncology 2011 Jul 5;8(8):449-50. doi: 10.1038/nrclinonc.2011.103. PMID: 21727931.
  24. Telang S, Rasku MA, Clem AL, Carter K, Klarer AC, Badger WR,  Milam RA, Rai SN, Pan J, Gragg H, Clem BF, McMasters KM, Miller DM, Chesney J.  Phase II trial of the regulatory T cell-depleting agent, denileukin diftitox, in patients with unresectable stage IV melanoma.  BMC Cancer 11(1):515-523, 2011.  PMID: 22165955; PMCID: PMC3293785.
  25. Natarajan N, Telang S, Miller D, Chesney J.  Novel immunotherapeutic agents and small molecule antagonists of signalling kinases for the treatment of metastatic melanoma. Drugs 2011 Jul 9;71(10):1233-50. doi: 10.2165/11591380-000000000-00000. Review. PMID: 21770473.
  26. Wolchok JD, Neyns B, Linette G, Negrier S, Lutzky J, Thomas L, Waterfield W, Schadendorf D, Smylie M, Guthrie T Jr, Grob JJ, Chesney J, Chin K, Chen K, Hoos A, O'Day SJ, Lebbé C.  Ipilimumab monotherapy in patients with pretreated advanced melanoma: a randomised, double-blind, multicentre, phase 2, dose-ranging study.  Lancet Oncology 2010 Feb;11(2):155-64. doi: 10.1016/S1470-2045(09)70334-1. Epub 2009 Dec 8. PMID: 20004617.
  27. Jaglal MV, Laber DA, Arnold FW, Miller DM, Chesney JA, Kloecker GH.  Obtaining routine blood cultures during interleukin-2-containing therapy is unnecessary.  American Journal of Clinical Oncology 2009 Aug;32(4):429-31. doi: 10.1097/COC.0b013e31819142c7. PMID: 19451801.
  28. Khan MI, Chesney JA, Laber DA, Miller DM.  Digitalis, a targeted therapy for cancer?  American Journal of Medical Science 2009 May;337(5):355-9. doi: 10.1097/MAJ.0b013e3181942f57. Review. PMID: 19440057.
  29. Gajewski TF, Chesney J, Curriel TJ.  Emerging strategies in regulatory T-cell immunotherapies.  Clinical Advances in Hematology & Oncology 2009 Jan;7(1):1-10; quiz 11-2. Review. PMID: 19288606.
  30. Rasku MA, Clem AL, Telang S, Taft B, Gettings K, Gragg H, Cramer D, Lear SC, McMasters KM, Miller DM, Chesney J.  Transient T cell depletion causes regression of melanoma metastases.  Journal of Translational Medicine 2008 Mar 11;6:12. doi: 10.1186/1479-5876-6-12. PMID: 18334033; PMCID: PMC2330026.

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