One of our favorite physician pancreatic cancer researchers, Daniel Von Hoff, has been honored by induction into the Joshua Lederberg Society on February 13, 2014 primarily for his work in shepherding the development of Abraxane (nab-paclitaxel) in combination with gemcitabine for the treatment of advanced cancer of the pancreas. This award is presented by Celgene (which the late Dr. Lederberg, a Noble laureate, helped found) on the criteria of researchers whose work has changed the practice of medicine. Celgene produces Abraxane which is now approved for the treatment of pancreatic cancer.
Daniel Von Hoff is certainly one of the world’s foremost experts on pancreatic cancer. Presently, he is the Physician in Chief and Director of Translational Research at the Translational Genomics Research Institute (TGEN) in Phoenix. He is also the Chief Scientific Officer for US Oncology, and a Clinical Professor of Medicine at the University of Arizona.
Interestingly, in the mid-1990s Dr. Von Hoff led a team in key early clinical studies on the drug-agent gemcitabine for the treatment of advanced pancreatic cancer. The U.S. Food and Drug Administration (“FDA”) approved gemcitabine for the treatment of pancreatic cancer in 1996.
In the case of the more recent Abraxane plus gemcitabine work, Dr. Von Hoff functioned as the lead of an international consortium of 151 academic and community centers in eleven nations in Europe, including the United States and Australia. The study was called the Metastatic Pancreatic Adenocarcinoma Clinical Trial (MPACT), eventually evaluating the outcomes of 861 patients with advanced pancreatic cancer.
The results of the research from this Phase III clinical trial were published in the October 31, 2013 issue of the New England Journal of Medicine. Essentially, the combination regimen of gemcitabine and Abraxane demonstrated an improved survival benefit for patients with advanced pancreatic cancer over that of treatment with gemcitabine alone. The Pancreatica Blog has followed the results of this work Here, Here and Here. The combination of Abraxane plus gemcitabine for metastatic pancreatic cancer was approved by the FDA in September 2013. In December, the European Commission followed suit.
Dr. Von Hoff took his undergraduate degree at Carroll College in Montana, and his MD from the Columbia University College of Physicians and Surgeons in New York. He took residency at UCSF and completed a Fellowship in oncology at the U.S. National Cancer Institute.
Dr. Von Hoff is currently serving on the U.S. National Cancer Advisory Board. He is a past president of the American Association for Cancer Research (AACR). And he has served on the ASCO Board of Directors. He has received numerous awards in medicine. Dr. Von Hoff has to his credit the publication of two medical books, more than 135 book chapters and more than one thousand scientific papers.
Dale O’Brien, MD
Dr. Daniel Von Hoff
It seems pretty rare that we get humor associated with pancreatic cancer. Now comes a goofy and fun awareness video piece on Youtube from a sister pancreatic cancer nonprofit organization in the UK (“Pancreatic Cancer UK”).
Will it go viral? Will it ignite the next new dance fad? We can only hope. Our hat’s off to these fellow workers in the pancreatic cancer vineyard – kudos to them. There’s even a Twitter account devoted to this awareness video at #CanCan4PanCan.
Dale O’Brien, MD
As mentioned, stromal tissue can account for as much as 90% of the bulk in pancreatic cancer tumors. Thought in the past to have been relatively inert, it is increasingly clear that this dense tissue arising from a desmoplastic process is surprisingly dynamic. Thus, it is heartening to encounter a number of recent serious research efforts aimed in a practical way to begin to try to counteract the effects of the pancreatic cancer stromal tissue in ameliorating the effects of standard treatment modalities. We have commented on two of these previous studies HERE and HERE.
Grose and colleagues from the Centre for Tumour Biology Barts Cancer Institute at Queen Mary University of London E-published the results of their pre-clinical work on February 6, 2014 in the open journal EMBO – Molecular Medicine. They studied the fibroblast system that is active in the desmoplasic process resulting in the creation of pancreatic cancer tumor stromal tissue, with particular attention to the fibroblast growth factor (FGF) signalling cascade which appears to be active in pancreatic cancer cell survival and invasion.
FGFs and their receptors are frequently overexpressed in pancreatic cancer, as well as in a number of other tumor types. The researchers particularly looked at FGF1 and FGF2 and their receptors. The respective receptors are notated as FGFR1 and FGFR2. FGF2 over-expresion appears to be correlated with poor patient outcome in pancreatic cancer.
The authors demonstrate that blocking nuclear aspects of FGFR1 and FGFR2 appears to interrupt fibroblast proliferation, thus disrupting the pancreatic cancer “microenvironment.” The practical effect of this mechanism is that pancreatic cancer cell invasion is thwarted. The authors postulate that inhibiting the fibrogen growth factor cascade by therapeutic agents may target the pancreatic cancer stroma in a manner that interferes with the natural history of pancreatic cancer and thus could enhance patient outcomes.
This is another interesting and promising piece of the puzzle.
Dale O’Brien, MD