Daniel Von Hoff

Daniel Von Hoff, M.D., F.A.C.P.

TGen Clinical Translational Research Division

TGen Drug Development (TD2) team

Daniel D. Von Hoff, M.D., F.A.C.P. is a medical oncologist and oncology drug developer who has conducted national clinical trials with more than 200 new antineoplastic and biologic agents.

Dr. Von Hoff's major interest is in the development of new anticancer agents, both in the clinic and in the laboratory. Dr. Von Hoff and his colleagues have conducted early clinical investigations of most of the new agents that have been approved for cancer treatment in the United States in the last two decades, including gemcitabine, docetaxel, paclitaxel, topotecan, irinotecan, fludarabine, mitoxantrone, dexrazoxane, nab-paclitaxel, and multiple others.

At present, he and his colleagues are concentrating on the development of molecularly targeted therapies for individual patients with cancer.

For more than 30 years, Dr. Von Hoff has dedicated his time and experience to the study of cancer and treatment methods. Among his significant activities:

• International leadership in bringing to patients new anti-cancer agents – many of which have been shown to increase patient survival.
• Study of pancreatic and other forms of cancer.
• Dedication to teaching the next generation of both basic and clinical students.
• Entrepreneurial research efforts, which have led to 12 patents.

Dr. Von Hoff most recently served a six-year term on President Bush's National Cancer Advisory Board (June 2004 - March 2010) and has served on the FDA’s Oncology Advisory Committee. He is the past President of the American Association for Cancer Research (the largest cancer research organization in the world), a Fellow of the American College of Physicians, and a member and past board member of the American Society of Clinical Oncology.

Career

Daniel D. Von Hoff, M.D., F.A.C.P., has devoted his career to translational medicine, which is defined as movement of new therapies from the research institution into patient care. He currently serves as Physician-in-Chief and Distinguished Professor of the Translational Genomics Research Institute (TGen); Professor of Medicine at both Mayo Clinic, Scottsdale and the University of Arizona College of Medicine; and Chief Scientific Officer at Scottsdale Healthcare and US Oncology and Clinical Professor of Medicine at the University of Arizona. In addition, he provides expertise as a founder or medical/scientific advisor to a broad range of companies working toward a cure for cancer.

After graduating cum laude from Carroll University, Dr. Von Hoff received his M.D. from Columbia University College of Physicians and Surgeons. He completed his internship and residency in internal medicine at the University of California, San Francisco, then completed a medical oncology fellowship at the National Cancer Institute. Dr. Von Hoff then moved to the University of Texas Health Science Center at San Antonio, where he rose to Professor in the Department of Medicine and the Department of Cellular and Structural Biology. In 1989, Dr. Von Hoff became the Founding Director of the Institute for Drug Development at the Cancer Therapy and Research Center in San Antonio. In 1999, he became Director of the Cancer Center and Professor of Medicine at the University of Arizona.

Dr. Von Hoff has served as editor of numerous scientific publications. He is founder and Editor Emeritus of “Investigational New Drugs: The Journal of New Anticancer Agents” as well as the founding and current Editor-in-Chief of “Molecular Cancer Therapeutics”. Previously he was the associate editor of “Cancer Research” and “Clinical Cancer Research”. Dr. Von Hoff has also served on the editorial boards of the “American Journal of Medicine”, “Anticancer Drugs”, “Oncology”, “Annals of Oncology”, and nine other scientific journals.

He is a Fellow of the American College of Physicians, and has been a member of the Board of Directors of the American Society of Clinical Oncology (ASCO) and AACR, as well as a member of the FDA's Oncology Drug Advisory Committee (ODAC).

He co-founded ILEX™ Oncology, Inc. (acquired by Genzyme). The ILEX team got two 2 new anti-cancer agents approved by the FDA, including Clolar (clofarabine) for children with leukemia and Campath (alemtuzumab) for patients with chronic lymphocytic leukemia. Campath is also now included in trials for patients with multiple sclerosis.

Clinical Interests

Dr. Von Hoff's major interest is in the development of new anticancer agents, both in the clinic and in the laboratory. He and his colleagues were involved in the beginning of the development of many of the agents used in cancer therapy, including the first drug to improve survival for patients with pancreatic cancer — gemcitabine.

As the Physician-in-Chief and Distinguished Professor at TGen, Dr. Von Hoff and his team are focused on targeted new anti-cancer agents. They currently have 26 new agents in phase I or II trials. The mechanisms of action in these agents are targeted toward specific abnormalities in a particular patient's tumor (individualized therapeutics). Their lab research is focused on genetic and biochemical approaches to identify molecular targets for the development of new therapies for patients with pancreatic cancer, which has the worst survival rate of any cancer and is the fourth leading cause of cancer deaths in the United States. Their approach is the development of targeted therapies based on distinguishing characteristics of pancreatic cancer cells versus normal cells.

In 2010, Stand Up To Cancer selected Dr. Von Hoff and Dr. Craig Thompson to lead the pancreatic cancer Dream Team.

This powerhouse team is building on a common idea in cancer research - "starve" cancer cells to death by depriving them of a specific nutrient that they require for survival. Most cancer cells become addicted to a continual supply of specific nutrients to produce the energy needed for survival and proliferation. In addition, the Dream Team is trying to eliminate the fibrosis, or scar tissue, around the pancreatic cancer cells to allow penetration of therapies and of the immune cells. The Team is testing drugs in combination with existing standard chemotherapy, with the hope to increase the percentage of pancreatic cancer patients surviving beyond one year while improving quality of life.

Working closely with the TGen Foundation and the Pancreatic Cancer Research Team (PCRT), Dr. Von Hoff helped launch globalCure, an effort to improve treatment and one day find a cure for pancreatic cancer. The backbone of globalCure is an alliance between TGen and PCRT, which includes leading pancreatic cancer scientists, physicians and researchers, armed with the most technologically advanced tools and resources, at 46 institutions worldwide. Funds generated through globalCure will enable an international team of physicians to move quickly on promising new clinical therapies. Specifically, the funds will enable globalCure supported scientists and clinicians to identify biomarkers of diagnostic value, as well as those that constitute new drug targets in pancreatic cancer; identify and optimize new agents that affect the activity of those targets; and evaluate new agents and take the most promising ones to clinical trials for patients in advanced stages of the disease.

Awards

Dr. Von Hoff is the recipient of numerous awards and honors for his patient care, teaching accomplishments and clinical investigation, including the highest award given for clinical investigation by the American Society of Clinical Oncology (ASCO), the 2010 David A. Karnofsky Memorial Award and Lecture ASCO, the 2001 Scripps Genomic Medicine Award, the Maurice M. Burkholder Lectureship in Oncology, the Grant Award “Stand Up To Cancer Dream Team” – “Cutting Off the Fuel Supply: A New Approach to the Treatment of Pancreatic Cancer”, Stand Up to Cancer the Arizona Business Magazine Health Care Leadership Award, 2009, the William F. McWhortor Community Service Leader of the Year, the Todd H. Wasserman Lectureship in Translational Research for Washington University Alumni, The Joel M. Childers, MD – 7th Annual Memorial Lecture Series , the 2003 Block Award and The Weinberg Award, presented by the Dana Farber Cancer Center, Harvard Medical School. He has received the Frederick S. Philips Lectureship from Memorial Sloan-Kettering Cancer Center, the Michel Clavel Lectureship from the European Organization for Research and Treatment of Cancer (EORTC), and the Bagshawe Lectureship from the British Association for Cancer Research. In 1997, Dr. Von Hoff received the Richard and Hilda Rosenthal Foundation Award from AACR and was elected President of that organization for 1999-2000.

Scientific and Medical Advisory Roles

Dr. Von Hoff has founded and serves as a medical and scientific advisor to a broad range of companies working toward a cure for cancer.

Publications

Dr. Von Hoff has published more than 135 book chapters, 2 books, and more than 1000 scientific publications. His most important peer-reviewed publications include:

• Lorusso, P. M.; Rudin, C. M.; Reddy, J. C.; Tibes, R.; Weiss, G. J.; Borad, M. J.; Hann, C. L.; Brahmer, J. R. et al. (2011). "Phase I trial of hedgehog pathway inhibitor GDC-0449 in patients with refractory, locally-advanced or metastatic solid tumors". Clinical Cancer Research. doi:10.1158/1078-0432.CCR-10-2745. 
• Graham, R. A.; Lum, B. L.; Cheeti, S.; Jin, J. Y.; Jorga, K.; Von Hoff, D. D.; Rudin, C. M.; Reddy, J. C. et al. (2011). "Pharmacokinetics of hedgehog pathway inhibitor GDC-0449 in patients with locally-advanced or metastatic solid tumors: the role of alpha-1-acid glycoprotein binding". Clinical Cancer Research. doi:10.1158/1078-0432.CCR-10-2736. 
• Tibes, Raoul; Piper, Barbara F.; Smith, Jessica A.; James, Raysenia L.; Benjamin, Martin A.; Yim, Jay H.; Ramanathan, Ramesh K.; Von Hoff, Daniel D. et al. (2011). "Patient willingness to undergo pharmacodynamic and pharmacokinetic tests in early phase oncology trials". Cancer: n/a. doi:10.1002/cncr.25885. PMID 21246533. 
• Von Hoff, D. D.; Stephenson, J. J.; Rosen, P.; Loesch, D. M.; Borad, M. J.; Anthony, S.; Jameson, G.; Brown, S. et al. (2010). "Pilot Study Using Molecular Profiling of Patients' Tumors to Find Potential Targets and Select Treatments for Their Refractory Cancers". Journal of Clinical Oncology 28 (33): 4877–83. doi:10.1200/JCO.2009.26.5983. PMID 20921468. 
• Weiss, Glen J.; Alarcon, Arlet; Halepota, Maqbool; Penny, Robert J.; Von Hoff, Daniel D. (2010). "Molecular characterization of interdigitating dendritic cell sarcoma". Rare Tumors 2. doi:10.4081/rt.2010.e50. 
• Galsky, Matthew D.; Von Hoff, Daniel D.; Neubauer, Marcus; Anderson, Thomas; Fleming, Mark; Nagarwala, Yasir; Mahoney, Janine M.; Midwinter, Dawn et al. (2010). "Target-specific, histology-independent, randomized discontinuation study of lapatinib in patients with HER2-amplified solid tumors". Investigational New Drugs. doi:10.1007/s10637-010-9541-0. 
• Colvin, Joshua; Monine, Michael I; Gutenkunst, Ryan N; Hlavacek, William S; Von Hoff, Daniel D; Posner, Richard G (2010). "RuleMonkey: software for stochastic simulation of rule-based models". BMC Bioinformatics 11: 404. doi:10.1186/1471-2105-11-404. PMC 2921409. PMID 20673321. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2921409. 
• Schwartz, D. L.; Bankson, J. A.; Lemos, R.; Lai, S. Y.; Thittai, A. K.; He, Y.; Hostetter, G.; Demeure, M. J. et al. (2010). "Radiosensitization and Stromal Imaging Response Correlates for the HIF-1 Inhibitor PX-478 Given with or without Chemotherapy in Pancreatic Cancer". Molecular Cancer Therapeutics 9 (7): 2057–67. doi:10.1158/1535-7163.MCT-09-0768. PMC 2935253. PMID 20587661. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2935253. 
• Weiss, G J; Von Hoff, D D (2010). "Hunting the Hedgehog Pathway". Clinical Pharmacology & Therapeutics 87 (6): 743–7. doi:10.1038/clpt.2010.34. 
• Goldberg, L. H.; Firoz, B. F.; Weiss, G. J.; Blaydorn, L.; Jameson, G.; Von Hoff, D. D. (2010). "Basal Cell Nevus Syndrome: A Brave New World". Archives of Dermatology 146 (1): 17–9. doi:10.1001/archdermatol.2009.322. PMID 20083687. 
• Ramesh, A; Trevino, R; Von Hoff, DD; Kim, S (2010). "Clustering context-specific gene regulatory networks". Pacific Symposium on Biocomputing: 444–55. PMID 19908396. 
• Mahadevan, Daruka; Dreisbach, Luke; Kristedja, Timothy; Williams, Debbie; Obregon, Yrma; Kurtin, Sandy; Von Hoff, Daniel D. (2009). "Phase I Study of Fixed Dose Gemcitabine Plus Epirubicin in Patients With Advanced Solid Malignancies". American Journal of Clinical Oncology 32 (6): 607–11. doi:10.1097/COC.0b013e31819cc9ed. PMID 19593083. 
• Sonpavde, Guru; Aparicio, Ana M.; Zhan, Feng; North, Brittany; Delaune, Robert; Garbo, Lawrence E.; Rousey, Steven R.; Weinstein, Ralph E. et al. (2009). "Azacitidine favorably modulates PSA kinetics correlating with plasma DNA LINE-1 hypomethylation in men with chemonaïve castration-resistant prostate cancer". Urologic Oncology: Seminars and Original Investigations. doi:10.1016/j.urolonc.2009.09.015. 
• Warner, S. L.; Stephens, B. J.; Nwokenkwo, S.; Hostetter, G.; Sugeng, A.; Hidalgo, M.; Trent, J. M.; Han, H. et al. (2009). "Validation of TPX2 as a Potential Therapeutic Target in Pancreatic Cancer Cells". Clinical Cancer Research 15 (21): 6519–28. doi:10.1158/1078-0432.CCR-09-0077. PMC 2783218. PMID 19861455. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2783218. 
• Von Hoff, Daniel D.; Lorusso, Patricia M.; Rudin, Charles M.; Reddy, Josina C.; Yauch, Robert L.; Tibes, Raoul; Weiss, Glen J.; Borad, Mitesh J. et al. (2009). "Inhibition of the Hedgehog Pathway in Advanced Basal-Cell Carcinoma". New England Journal of Medicine 361 (12): 1164–72. doi:10.1056/NEJMoa0905360. PMID 19726763. 
• Rudin, Charles M.; Hann, Christine L.; Laterra, John; Yauch, Robert L.; Callahan, Christopher A.; Fu, Ling; Holcomb, Thomas; Stinson, Jeremy et al. (2009). "Treatment of Medulloblastoma with Hedgehog Pathway Inhibitor GDC-0449". New England Journal of Medicine 361 (12): 1173–8. doi:10.1056/NEJMoa0902903. PMID 19726761. 
• Cai, Xuemei; Gray Jr., Phillip J.; Von Hoff, Daniel D. (2009). "DNA minor groove binders: Back in the groove". Cancer Treatment Reviews 35 (5): 437–50. doi:10.1016/j.ctrv.2009.02.004. PMID 19328629. 
• Von Hoff, Daniel D.; Korn, Ron; Mousses, Spyro (2009). "Pancreatic Cancer—Could It Be that Simple? A Different Context of Vulnerability". Cancer Cell 16 (1): 7–8. doi:10.1016/j.ccr.2009.06.011. PMID 19573807. 
• Wang, Hong; Stephens, Bret; Von Hoff, Daniel D.; Han, Haiyong (2009). "Identification and Characterization of a Novel Anticancer Agent With Selectivity Against Deleted in Pancreatic Cancer Locus 4 (DPC4)-Deficient Pancreatic and Colon Cancer Cells". Pancreas 38 (5): 551–7. doi:10.1097/MPA.0b013e31819d7415. PMID 19276868. 
• Azorsa, David O; Gonzales, Irma M; Basu, Gargi D; Choudhary, Ashish; Arora, Shilpi; Bisanz, Kristen M; Kiefer, Jeffrey A; Henderson, Meredith C et al. (2009). "Synthetic lethal RNAi screening identifies sensitizing targets for gemcitabine therapy in pancreatic cancer". Journal of Translational Medicine 7: 43. doi:10.1186/1479-5876-7-43. PMC 2702280. PMID 19519883. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2702280. 
• Sonpavde, Guru; Galsky, Matthew D.; Hutson, Thomas E.; Von Hoff, Daniel D. (2009). "Patient Selection for Phase II Trials". American Journal of Clinical Oncology 32 (2): 216–9. doi:10.1097/COC.0b013e318172dccd. PMID 19346816. 

References

• American Association for Cancer Research (April 15, 2008). /releases/2008/04/080414161050.htm "Skin Cancer Breakthrough? New Molecule Shows Promise In Patients With Advanced Basal Cell Carcinoma". ScienceDaily. http://www.sciencedaily.com /releases/2008/04/080414161050.htm. Retrieved April 7, 2011. 
• "Dan Von Hoff, M.D., biography". Retrieved April 22, 2008.
• TGen Research Overview. TGen press room, retrieved 4/27/08.
• "Genta Announces Election of Distinguished Cancer Specialist, Dr. Daniel D. Von Hoff, to Board of Directors", PR NewsWire, January 18, 2000. Retrieved 3/28/08.
• Molecular Cancer Therapeutics Editorial Board Listing - American Association of Cancer Research Journals, retrieved 4/30/08.
• "UA Professor Daniel D. Von Hoff MD accepts additional role as Director of Translational Drug Development at TGen" TGen press room, October 16, 2003. Retrieved 4/29/08.
• "TGen’s Von Hoff, colleagues, publish comprehensive pancreatic cancer textbook" TGen press room, May 17, 2005. Retrieved 4/29/08.
• TGen Research Overview. TGen press room, retrieved 4/15/08.

• $18 million awarded to TGen and University of Pennsylvania for pancreatic cancer research from Stand Up to Cancer

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