Combining gemcitabine with MRK003, an experimental drug, triggers a chain of events leading to pancreatic cancer cell death, researchers from Cambridge reported in the Journal of Experimental Medicine. The researchers explained that when the two drugs are combined, the effect of each one is multiplied, thus intensifying the destruction of pancreatic cancer cells.
Professor David Tuveson, from the Cambridge Research Institute, UK, and team demonstrated in animal studies that MRK003, an experimental medication, when combined with chemotherapy medication gemcitabine, set off a domino effect which ultimately destroyed the malignant cells.
The drug combo is being used in a human study, a clinical trial, which is being managed by Cambridge University Hospitals Foundation Trust, together with Cancer Research UK's Drug Development Office.
MRK003 is a gamma secretase inhibitor. It inhibits, or blocks a crucial cell signaling pathway in both pancreatic cancer cells and the cells in the lining of blood vessels that supply the tumor with vital nourishment (endothelial cells).
The researchers found that when MRK003 is added to gemcitabine, the chemotherapy drug's ability to destroy tumors was significantly enhanced. Gemcitabine is a nucleoside analog, which is marketed as Gemzar by Eli Lilly. Gemcitabine is commonly used in pancreatic cancer therapy, as well as non-small cell lung cancer, bladder cancer and breast cancer.
Professor Tuveson said:
"This research is a real example of how research taking place in the lab directly influences decisions made in the clinic to improve treatment for patients.
We've discovered why these two drugs together set off a domino effect of molecular activity to switch off cell survival processes and destroy pancreatic cancer cells."
Professor Duncan Jodrell, who is leading the clinical trial, said:
"We're delighted that the results of this important research are now being evaluated in a clinical trial, to test whether this might be a new treatment approach for patients with pancreatic cancer, although it will be some time before we're able to say how successful this will be in patients."
Duncan Jodrell is Professor of Cancer at the University of Cambridge.
A man named Richard Griffiths, a 41 year old father of two, was diagnosed with pancreatic cancer in May 2011, and has been a part of the trial ever since. He said:
"Being told that I had cancer was devastating and it immediately made me worry about the future. I have a close group of family and friends and I have had great support from this network, and my work has been very supportive too.
After I was diagnosed, I was told about the trial and came to Cambridge to meet the team. I was given a lot of information and agreed to take part in this trial. I was mentioned that it was funded by Cancer Research UK and, as I go through treatment, I have really come to appreciate how important that money is.
After six cycles of treatment, a scan showed the tumors had reduced and so I have continued with the treatment. The trial gives you hope - I really feel I can do this with the science behind me."
Pancreatic cancer is the 5th most deadly cancer in the UK, with about 8,000 people being diagnosed with the cancer each year. Only 1 in 5 pancreatic cancer patients usually survive a year after their diagnosis, however, the numbers have more than doubled in survivors since the 1970's. Senior science information manager at Cancer Research, UK, Dr. Julie Sharp commented:
"This discovery shows how investigating the cell pathways involved in cancer can reveal new approached to tackle the disease. There's an urgent need for new drugs for pancreatic cancer. The disease is often not diagnosed until it has spread, making it very difficult to treat.
Cancer Research UK previously funded the largest ever trial for people with operable pancreatic cancer, which led to a worldwide change in the way the disease is treated, helping to improve survival. But there is much more to be done.
We're prioritizing research into pancreatic cancer, and other cancers where survival still remains low, aiming to save more lives in the future."
Written By Christian Nordqvist