Translational Genomics Research Institute (TGen)

Phoenix, Arizona
Physician in Chief and Distinguished Professor, TGen
Professor of Medicine, Mayo Clinic
Professor of Medicine, University of Arizona College of Medicine
Chief Scientific Officer, Virginia G. Piper Cancer Center at Scottsdale Healthcare

Research

Dr. Von Hoff is a pioneer and world leader in translational medicine, accelerating novel drug discoveries from the laboratory to cancer treatments in clinical trials. He has personally been involved in over 200 clinical trials. In 1985, when his NFCR grant support began, his research led to the first approved treatment for pancreatic cancer, the chemotherapy gemcitabine. Resistance to pancreatic cancer therapies results in poor survival. His current research involves developing precision therapies for pancreatic cancer patients, by identifying the role of different pancreatic cancer cell populations in resistance to therapy.

Recently, he discovered that pancreatic tumors express scar-forming cells called fibroblasts that protect cancer cells from immune system attack. This has furthered our understanding of signaling pathways in the tumor microenvironment to exploit and make tumors more susceptible to attack and cell death. Dr. Von Hoff’s team identified one such pathway, known as the EMT pathway, that makes tumor cells more aggressive and resistant to many chemotherapeutics. He also discovered that pancreatic cancer cells expressing the EMT pathway respond better to a sequential regimen of chemotherapy and an EMT inhibitor. Dr. Von Hoff demonstrated that first treating patients with chemotherapy resulted in killing most pancreatic cancer cells and subsequent treatment with EMT inhibitors killed the remaining drug resistant EMT-positive pancreatic cancer cells. His laboratory is currently developing this regimen for a clinical trial to provide precision oncology therapy for pancreatic cancer patients.

Bio

Daniel Von Hoff, M.D., attended Carroll College and Columbia University before conducting his residency in internal medicine at UC San Francisco. After that, he had a fellowship in oncology at the National Cancer Institute before joining the faculty at the University of Texas Health Science Center as a professor of medicine and cellular and structural biology. Dr. Von Hoff went on to become the founding director of the Institute for Drug Development at the Cancer Therapy and Research Center and director of the cancer center at the University of Arizona.

Dr. Von Hoff’s major interest is in the development of new anticancer agents, both in the clinic and in the laboratory.

Throughout his career, Dr. Von Hoff has published more than 650 papers, 140 book chapters and 1,000 abstracts. Dr. Von Hoff was selected as a 2016 Giant of Cancer Care® by OncLive, honored with the Scripps Genomic Medicine Award in 2011, named one of the American Society of Clinical Oncology 50 Oncology Luminaries in 2014 and among the first class selected in 2013 by the American Association for Cancer Research (AACR) for its Fellows of the AACR Academy.

In addition to leading the NFCR Center for New Therapy Development (2001-2006) and the NFCR Center for Targeted Cancer Therapies (2007-2017), Dr. Von Hoff was appointed to President Bush’s National Cancer Advisory Board from 2004-2010, is the past President of AACR, a Fellow of the American College of Physicians and a member and past board member of the American Society of Clinical Oncology.  He is also the founder and the Editor Emeritus of Investigational New Drugs – The Journal of New Anticancer Agents and past Editor-in-Chief of Molecular Cancer Therapeutics.

Related Content

Don’t Delay: Skipping One Mammogram Can Significantly Increase Risk of Death from Breast Cancer

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Controlling the Uncontrollable: HER2 Breast Cancer

It’s that time of year when pink ribbons begin appearing everywhere – from shopfronts to social media. These ribbons are known to be Breast Cancer Awareness ribbons. It’s no coincidence that pink ribbons are the most easily recognized as breast cancer is the most common cancer in women worldwide. In fact, one in eight women will be diagnosed with breast cancer.  Tragically, the likelihood of experiencing metastasis, or cancer that spreads to other parts of the body, is high amongst these patients. Understanding and preventing metastasis is crucial to increasing the survival rates of this disease. Thankfully, National Foundation for Cancer Research (NFCR)-funded researcher Dr. Rakesh K. Jain and his team are dedicated to exploring this phenomenon and recently unearthed a game-changing discovery.  Their mission: HER2 Dr. Jain and his team knew that genes contain the recipes for various proteins required for healthy cells to function properly and that some genes and proteins can influence how breast cancer behaves and responds to treatment. They were particularly interested in exploring how to control and inhibit metastasis in one particular gene related to breast cancer, the HER2 gene.  The HER2 (human epidermal growth factor receptor 2) gene makes HER2 proteins, which are receptors on breast cells. Typically, HER2 receptors help control how a healthy breast cell grows, divides, and repairs itself. But in about 10% to 20% of breast cancers, the HER2 gene doesn’t work correctly and makes too many copies of itself (known as HER2 gene amplification). These extra HER2 genes tell breast cells to make too many HER2 receptors which makes breast cells grow and divide in an uncontrolled way. Patients with metastatic HER2+ breast cancer often experience treatment resistance, disease recurrences, and metastases. Dr. Jain and his team believed that by modifying the tumor framework and increasing oxygenation in the tumor, it might be possible for an existing medication to improve the outcome of radiotherapy and inhibit disease progression in a highly metastatic HER2+ breast cancer. Their findings The team established a metastatic HER2+ breast cancer line and used it to generate a similar environment in mice. Three days after tumor implantation, Dr. Jain and his team administered seven days of Losartan, a drug mainly used to treat high blood pressure. In some mice, the research team followed the seven days of Losartan with 20 Gy single dose local irradiation on day 10. In a third group, they followed the seven days of Losartan with 20 Gy fractionated irradiation on days 10-14. For each group, the researchers analyzed the tumor-growth delay, development of metastases, survival rates, tumor density, and oxygen levels in the tumor.  Much to the excitement of cancer researchers worldwide, the combination of Losartan and local irradiation significantly enhanced tumor response. The tumors were deprived of oxygen, whereas healthy cells remained oxygen-rich. This finding suggests that combining Losartan with radiotherapy is a potential new treatment strategy for controlling and inhibiting metastasis in HER2+ breast cancer – a potentially life-saving discovery. Other exciting HER2 discoveries  HER2 has been a hot topic in the cancer world for years. In fact, Dr. Jain is just one of the NFCR-funded researchers paving the way to better treatment options related to HER2. Dr. […]

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