Tag Archives: Dr. Daniel D. Von Hoff

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TGen finds genes linked to pancreatic cancer survival

A study by the Translational Genomics Research Institute (TGen) and other major research institutes, found a new set of genes that can indicate improved survival after surgery for patients with pancreatic cancer. The study also showed that detection of circulating tumor DNA in the blood could provide an early indication of tumor recurrence.

In conjunction with the Stand Up To Cancer (SU2C) Pancreatic Cancer Dream Team, the study was published in the prestigious scientific journal Nature Communications.

Using whole-exome sequencing — looking at the DNA protein-coding regions of 24 tumors — and targeted genomic analyses of 77 other tumors, the study identified mutations in chromatin-regulating genes MLL, MLL2, MLL3 and ARID1A in 20 percent of patients associated with improved survival.

In addition, using a liquid biopsy analysis, the study found that 43 percent of pancreatic cancer patients had circulating tumor DNA (ctDNA) in their bloodstream at the time of diagnosis.

Very importantly, the study also found that detection of ctDNA following surgery predicts clinical relapse of the cancer and poor outcomes for patients. In addition, using a liquid biopsy detected the recurrence of cancer 6.5 months earlier than using CT imaging.

“These observations provide predictors of outcomes in patients with pancreatic cancer and have implications for detection of tumor recurrence, and perhaps someday for early detection of the cancer,” said Dr. Daniel D. Von Hoff, TGen Distinguished Professor and Physician-In-Chief, Co-Director of TGen’s SU2C Pancreatic Cancer Dream Team, and Chief Scientific Officer at the Virginia G. Piper Cancer Center Clinical Trials at HonorHealth (formerly Scottsdale Healthcare). Dr. Von Hoff was one of the authors of the study.

The pancreatic cancers analyzed in the study were stage II tumors from patients who underwent potentially curative surgery. Only 15-20 percent of patients are candidates for tumor resection, because pancreatic cancer is difficult to detect and usually is not diagnosed until its late stages when surgery is no longer an option. The 5-year survival rate for those diagnosed with pancreatic cancer is less than 10 percent.

The study’s results found that a significant number of early-stage pancreatic cancers could be diagnosed non-invasively using liquid biopsy blood analysis that focuses on a few specific genetic alterations.

“We have identified MML genes as markers of improved prognosis for patients with pancreatic cancer,” Dr. Von Hoff said. “We have also shown that ctDNA in the blood of pancreatic cancer patients may provide a marker of earlier detection of recurrence of the disease.”

The study — Clinical implications of genomic alterations in the tumor and circulation of pancreatic cancer patients — was published July 7.

This analysis suggests that additional studies should “evaluate more intensive therapies” for patients without MLL mutations or with detectable ctDNA following surgical removal of their tumors, as well as interventional clinical trials, the study said.

Other participants in this study included: Johns Hopkins University School of Medicine, Mayo Clinic, and Memorial Sloan Kettering Cancer Center.

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TGen begins Zebrafish pancreatic cancer studies

For more than a decade, a glassy striped fish smaller than a door key has proved an important model organism in scientific research. Named for the uniform horizontal stripes on the side of its body, the zebrafish is a tiny creature that packs a punch in terms of biological similarities with the human.

Today, scientists at the Translational Genomics Research Institute (TGen) are using zebrafish to accelerate investigations of pancreatic cancer, the nation’s fourth-leading cause of cancer-related death.

TGen researchers believe the zebrafish can aid in the search for therapeutics that could help slow down, and even reverse, the growth and spread of cancer in pancreatic cancer patients.

Amazingly, this tiny fish shares about 70 percent of the genetic code of humans, has genetic similarities for the overwhelming majority of genes that cause human disease, grows to maturity in a matter of weeks, and are relatively inexpensive to manage.

Importantly, because of their transparent scales, they can provide a window into the real-time development of cancer tumors.

“With a microscope, you can see what is wrong without having to dissect it,” said Dr. Haiyong Han, a TGen Associate Professor, head of TGen’s Pancreatic Cancer Research Unit. “You can see the tumor just by looking into the fish.”

Zebrafish are vertebrates, so they have organs similar to people, including a pancreas, an organ near the stomach that produces digestive juices and several key hormones.

Genes are responsible for creating proteins. An altered gene disrupts the associated proteins, including those that lead to cancer. By studying altered genes in zebrafish, TGen researchers can monitor the initiation, growth and fatal effects of pancreatic tumors, including their spread to other organs.

Even though they are small, zebrafish are relatively complex organisms, allowing researchers to use them to mimic problems, and solutions, in people. And because zebrafish achieve maturity within about 3 months, researchers can compress the time otherwise needed to study tumor development.

“Where it would take months or years in a human, it only takes days or weeks to see the tumor growth in zebrafish,” said Dr. Daniel D. Von Hoff, TGen’s Distinguished Professor and Physician-In-Chief. “This is going to be of tremendous benefit for our scientific investigations, and ultimately for our patients.”

Care of the zebrafish is overseen by an Institutional Animal Care and Use Committee, or IACUC, which reviews all testing procedures and ensures the humane treatment of the fish throughout their lifecycle.

This year, nearly 49,000 Americans will be diagnosed with pancreatic cancer, and more than 40,000 will die from this disease. Median survival for patients with advanced disease is less than 6 months following diagnosis, and the 5-year survival rate is less than 6 percent for all patients.  

Pancreatic cancer’s lethal nature stems from its propensity to rapidly spread to distant organs. Because there is no early screening test, it usually is not diagnosed until its late stages, often when surgery is no longer an option, making it difficult to treat.

Dr. Han will monitor the growth and dissemination of tumors in the zebrafish and, specifically, look at the epithelial–mesenchymal transition (EMT), in which epithelial cells gain migratory and invasive characteristics.

This should help TGen investigators to better understand how pancreatic cancer invades local tissue, causing pain, and how it spreads to other organs — especially to the liver and lungs — which often is the actual cause of death in pancreatic cancer patients.

And because of low costs associated with maintaining zebrafish, investigators can conduct multiple studies in relatively short periods of time.

TGen’s zebrafish project is funded by the Seena Magowitz Foundation.

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Az Business honors winners of Healthcare Leadership Awards

Az Business magazine honored winners of the 2015 Healthcare Leadership Awards Thursday in front of a packed house at the Arizona Grand Resort.

“The Healthcare Leadership Awards honor the women, men and institutions whose passion and innovation are saving lives, extending lives, and improving the quality of our lives,” said Cheryl Green, publisher for AZ Big Media, which publishes Az Business magazine.

Sponsors included Blue Cross Blue Shield of Arizona, Arizona Central Credit Union and CodeRed-I.

Here are the winners of the 2015 Healthcare Leadership Awards:

Healthcare advocate/educator of the year: Catherine Ivy, Ben & Catherine Ivy Foundation

Behavioral health company of the year: Southwest Behavioral Health Services

Bioscience company of the year: VisionGate

Insurance provider of the year: Blue Cross Blue Shield of Arizona

Legal advocate of the year: Martin L. Shultz, Brownstein Hyatt Farber Schreck

Medical company of the year: SynCardia

Medical research company of the year: Barrow Neurological Institute

Researcher of the year: Dr. Daniel D. Von Hoff, TGen and HonorHealth

Physician of the year: Robert J. Arceci, M.D., Phoenix Children’s Hospital

Healthcare executive of the year: Tim Bricker, Chandler Regional and Mercy Gilbert medical centers

Medical center or hospital of the year: Cancer Treatment Centers of America at Western Regional Medical Center

Lifetime achievement award: Peter Fine, Banner Health

“The word visionary is thrown around often, but it’s not often that it really fits,” said Michael Gossie, editor in chief for Az Business magazine. “But that’s not the case with Peter Fine. He is a visionary. And it took a visionary to take two healthcare systems with very different histories and grow it into a healthcare company that generates more than $5 billion in annual revenue, operates 28 acute-care hospitals across seven states, and employs more than 45,000 employees in Arizona.”


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Az Business names Healthcare Leadership Awards finalists

Each year, AZ Business magazine hosts the Healthcare Leadership Awards to honor the women, men and institutions that bring excellence and innovation to Arizona’s healthcare sector.

Az Business is proud to announce the 2015 Healthcare Leadership Awards finalists, who were chosen by a panel of industry experts and will be recognized at the Healthcare Leadership Awards dinner and awards ceremony on April 9  at the Arizona Grand Resort. The finalists, in alphabetical order, are:

Abrazo Health — Arrowhead Hospital

Abrazo Health — Michele Finney

Affiliated Urologists — Dr. Mark Hong

Banner Health, Cardon Children’s Medical Center — Rachel Calendo

Banner Health — Peter Fine

Ben & Catherine Ivy Foundation — Catherine Ivy

Blue Cross Blue Shield of Arizona

Brownstein Hyatt Farber Schreck — Martin L. Shultz

Cancer Treatment Centers of America at Western Regional Medical Center

CTCA — Dr. Glen Weiss

Dedicated Health Solutions

Dignity Health — Barrow Neurological Institute

Dignity Health, Chandler Regional and Mercy Gilbert medical centers — Tim Bricker

Dignity Health — St. Joseph’s Hospital and Medical Center

HonorHealth and TGen — Dr. Daniel D. Von Hoff

HonorHealth – Virginia G. Piper Cancer Center

IASIS Healthcare — Tony Marinello

Insys Therapeutics

Magellan Health

Maricopa Integrated Health System — Dr. David Wisinger

Medtronic

Midwestern University — Kathleen Goeppinger

Quarles & Brady — Roger Morris

Phoenix Children’s Hospital – Dr. Robert J. Arceci

Radiant Research

Remuda Ranch

Snell and Wilmer – Richard Mallery

Sonora Quest Laboratories

Southwest Behavioral Health Services

SynCardia Systems

The CORE Institute — Dr. David Jacofsky

UnitedHealthcare of Arizona

University of Arizona Cancer Center

VisionGate

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TGen expert honored for cancer research

Dr. Daniel D. Von Hoff, who has been instrumental in developing numerous new cancer treatments, is among this year’s recipients of the Award of Excellence from the Hope Funds for Cancer Research.

Dr. Von Hoff, M.D., FACP, who is Physician-In-Chief and Distinguished Professor at the Translational Genomics Research Institute (TGen), and Chief Scientific Officer for Scottsdale Healthcare’s Virginia G. Piper Cancer Center Clinical Trials, will receive the 2014 Hope Funds Award of Excellence in Medicine.

The Hope Funds for Cancer Research is dedicated to advancing innovative research for the most difficult-to-treat cancers.

Dr. Von Hoff is being recognized for his work over the past decade in the clinical development of many new cancer treatments. He was nominated by past recipients, and selected by the Hope Funds Board of Trustees.

His accomplishments will be celebrated April 24 at the 2014 Award of Excellence Gala at The Metropolitan Museum of Art in New York. The gala provides support for programmatic activities and raises funds for postdoctoral fellowships in cancer research.

Dr. Von Hoff is a medical oncologist and oncology drug developer whose major interest is in the development of new anticancer agents. His clinical research is conducted at Virginia G. Piper Cancer Center Clinical Trials at Scottsdale Healthcare, a partnership between Scottsdale Healthcare and TGen in Scottsdale, Ariz.

Among the other five recipients of the 2014 Hope Funds Award is Nobel Prize Laureate Dr. James D. Watson, best known as the co-discoverer in 1953 of the double-helix structure of DNA, a scientific turning point in the understanding of life. Dr. Watson is receiving a special Award of Excellence for Extraordinary Achievement. Other recipients of this year’s Award of Excellence are: Dr. Tyler Jacks for Basic Science; Dr. Charles L. Sawyers for Clinical Development; and Dr. Jan Vilcek for Advocacy.

“With the occasion to celebrate the greatest living scientist of the 20th Century (Watson) along with this year’s Honorees, plus our past Honorees, this will be a gathering of many of the greatest minds in the field of cancer research,” Dr. Malcolm A.S. Moore, Chairman of the Board of Trustees for the Hope Funds for Cancer Research, said in a press release.

At the gala, Hope Funds will present its Awards of Excellence in recognition of outstanding achievements in the fields of basic research, drug development, medicine, patient support and philanthropy.

“This event, a white tie dinner set in the shadow of an ancient Egyptian temple, will highlight a remarkable group of scientists who are making a radical difference in cancer research. It is truly an extraordinary experience,” Bill Rueckert, Honorary co-chair of the 2014 Gala said in a press release.

Dr. Von Hoff and his colleagues have conducted early clinical investigations of many new cancer agents, including: gemcitabine, docetaxel, paclitaxel, topotecan, irinotecan, fludarabine, mitoxantrone, dexrazoxane, nab-paclitaxel, vismodegib, and others. These treatments are helping many patients with breast, ovarian, prostate, colon, leukemia, advanced basil cell and pancreatic cancers.

“I am truly honored to be included in the company of such distinguished physicians and scientists whose work has been furthered by the Hope Funds for Cancer Research,” said Dr. Von Hoff. “This recognition not only celebrates past accomplishments, but also is a reflection of the advances we are making right now for the benefit of our patients.”

He and his colleagues are concentrating on the development of molecularly targeted therapies for individual patients with cancer. His other major accomplishment is the development of two specific treatments, which have improved the survival for patients with advanced pancreatic cancer.

Dr. Von Hoff also is Professor of Medicine at both Mayo Clinic Scottsdale and the University of Arizona College of Medicine; and Chief Scientific Officer at US Oncology.

Dr. Von Hoff graduated cum laude from Carroll University, and 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 served a six-year term on President Bush’s National Cancer Advisory Board (2004-10).

He is a Fellow and past President of the American Association for Cancer Research (AACR), the world’s largest cancer research organization; a Fellow of the American College of Physicians; and a member and past board member of the American Society of Clinical Oncology (ASCO). Dr. Von Hoff is a founder of ILEX™ Oncology, Inc. (acquired by Genzyme after Ilex had 2 agents, alemtuzumab and clofarabine approved by the FDA for patients with leukemia). He received ASCO’s 2010 David A. Karnofsky Memorial Award for his outstanding contributions to cancer research leading to significant improvement in patient care.

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TGen’s Von Hoff inducted into Joshua Lederberg Society

Dr. Daniel D. Von Hoff, Distinguished Professor and Physician-In-Chief of the Translational Genomics Research Institute (TGen), was inducted into the Joshua Lederberg Society for his work in developing the drug Abraxane for advanced pancreatic cancer patients.

The Lederberg Society is named for the late Dr. Joshua Lederberg, a Nobel Prize laureate and leader in bacterial genetics whose expertise and guidance played a key role in the birth of Celgene, a global biopharmaceutical company that produces Abraxane.

Dr. Von Hoff, who is considered among the nation’s leading authorities on pancreatic cancer, will present a talk during his induction ceremony at 1 p.m. ET today at Celgene headquarters in Summit, N.J. This is the 7th induction ceremony of the Lederberg Society, which annually honors no more than two new members whose work has changed the practice of medicine.

“Dr. Von Hoff’s life long achievements in pancreatic cancer treatment and research are truly remarkable, but even more remarkable is his commitment to the patients who benefit from his tireless efforts on their behalf,” said Dr. Jeffrey Trent, TGen President and Research Director. “I can think of no one more deserving of this award than Dr. Von Hoff.”

Dr. Von Hoff was the principal investigator of MPACT (Metastatic Pancreatic Adenocarcinoma Clinical Trial), a multi-year international study involving 861 patients, at 151 community and academic centers in 11 nations in North America, Europe and Australia.

The study, whose findings were published Oct. 31 in the prestigious New England Journal of Medicine, found that Abraxane (nab-paclitaxel), when combined with the previous standard therapy, gemcitabine, significantly improved overall survival, progression-free survival, and drug response rates for patients with advanced pancreatic cancer. As a result of the study, the FDA on Sept. 6 approved Abraxane as a front-line therapy for such patients. In December, the European Commission also granted its approval.

“This is a new standard for treatment of metastatic pancreatic cancer that could become the backbone for other new treatment regimens,” said Dr. Von Hoff at the time of the FDA approval. “The fact that Abraxane plus gemcitabine demonstrated an overall survival benefit is a significant step forward in offering new hope for our patients.”

Abraxane wraps traditional chemotherapy, paclitaxel, in near-nano sized shells of albumin, a protein that the tumor could recognize as food. Once inside the tumor, the Abraxane may act like a “Trojan Horse” to release chemotherapy and kill the cancer cells.

Dr. Von Hoff also was the principal investigator for the first clinical trial of gemcitabine, the first therapy to show improvement in survival for patients with pancreatic cancer. The FDA approved gemcitabine in 1996.

The pancreas is a glandular organ behind the stomach that secretes enzymes to help digestion, and produces hormones, including insulin, which helps regulate blood-sugar metabolism.