Now comes a fascinating study by researchers from UC San Francisco and UC San Diego that tends to refute the common knowledge that pancreatic adenocarcinoma cells arise from genetic mutations in the PANCREATIC DUCT LINING CELLS.
Published in the November 29th 2012 issue of the journal Cancer Cell, Dr. Maike Sander and colleagues have shown that NON-ductal “acinar” cells in the non-hormone aspect of the pancreas can be transformed into what appear to be precursor cells to “ductal adenocarcinoma” (now a misnomer?) under the influence of mutations of the ductal gene Sox9, as accelerated by an additional mutation in the Kras oncogene.
Additionally, the researchers appear to demonstrate that ductal cells themselves tend to be somewhat resistant to the influence of oncogene mutation. These results may give direction to future research for both the treatment and earlier diagnosis of pancreatic cancer.
Dale O’Brien, MD
We discussed two recent studies on the apparent benefits of possible re-treatment of recurrent pancreatic cancer in our Pancreatica Blog entry of November 17, 2012. Now there are two more interesting medical articles on this subject that have been recently published.
Werner and colleagues from the University of Heidelberg (including Markus Buchler who is on our Science Board) in a March 1, 2013 study published in the Annals of Surgical Oncology offer that approximately 30% of pancreatic cancer recurrences are isolated and not associated with metastases. They identified almost 100 patients from 2001 until 2009 at their institution that presented with recurrence. Of the 57 with isolated local recurrence of cancer of the pancreas, 41 patients were eligible (by their criteria) for re-treatment surgery. They found that those patients who were eligible for and received such re-treatment lived significantly longer than those who were not able to receive this additional therapy.
Also, Combs and colleagues again from the University of Heidelberg (including Drs. Buchler, Werner, and two others from the above noted study) in a January 1, 2013 study published in the journal Radiation Oncology reported findings that indicated good treatment response with acceptable toxicity levels to chemoradiation (CRT) in select patients with recurrent pancreatic cancer. Additionally, in some of these patients with recurrent pancreatic cancer, the CRT allowed for additional surgical resection. These are early results and will need further substantiation by future research.
Dale O’Brien, MD
We’ve watched with interest as the pendulum has swung back and forth over the years on the possible efficacy of agents that block Vascular Endothelial Growth Factor (VEGF), a molecule that mediates angiogenesis (the vascular growth that occurs in tumors). Bevacizumab, a monoclonal antibody to VEGF, is known as Avastin and is manufactured by Genentech. It is approved in distinct circumstances for the treatment of colorectal, lung, kidney and brain cancers. One of Avastin’s side-effects in certain patients is high blood pressure.
The idea of Avastin is to interfere with the mechanism that allows for pancreatic cancer tumor growth and spread.
Researchers from Ohio State University recently published a study in the Annals of Oncology where they described their Phase II study that included adding bevacizumab to gemcitabine followed by an infusion of 5-FU to about forty patients with advanced pancreatic cancer. The progression-free survival at six months in this group was found to be 49% of the evaluable patients – which met their endpoint hypothesis of > 41%. They recommend further testing with this regimen in advanced pancreatic cancer “in combination with fluoropyrimidine-based therapy” (that is: 5-FU like). And they add an interesting side note suggestion for future researchers to see if the development of high blood pressure with this regimen (presumably from the Avastin) might be a sign of greater efficacy for those individual patients who do.
A past study which had not been so kind to the use of Avastin was the Phase III trial of the Cancer and Leukemia Group B, reported out in the Journal of Clinical Oncology in August, 2010.
“CONCLUSION: The addition of bevacizumab to gemcitabine does not improve survival in advanced pancreatic cancer patients.”
It is an interesting distinction: Avastin plus gemcitabine (2010 study – not promising) versus Avastin (plus gemcitabine) plus 5-FU (current more promising results) for advanced pancreatic cancer.
Dale O’Brien, MD