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Pancreatic Cancer Cells Destroyed with Drug Combination

Pancreatic cancer

When one drug doesn’t do the trick, sometimes a drug combination will. This appears to be the case in a new report on pancreatic cancer, in which researchers found that combining gemcitabine with an experimental drug MRK003 destroyed pancreatic cancer cells in animals, triggering a clinical trial in humans.

Pancreatic cancer challenges researchers

Despite rigorous research, pancreatic cancer continues to be a treatment challenge and the fourth deadliest cancer diagnosis in the United States. The year 2012 will see an estimated 43,920 new diagnoses of pancreatic cancer, and approximately 38,000 people will die of the disease.

Although most of the people diagnosed with pancreatic cancer are age 65 and older, the disease also affects younger people (e.g., Patrick Swayze, died at 57; Steve Jobs, at 56). Risk factors include smoking, diabetes, obesity, family history of pancreatic cancer, and having pancreatitis (inflamed pancreas) for a long time.

Several new treatment approaches for pancreatic cancer are being investigated around the world. One is being conducted and managed by researchers from Cambridge Research Institute and Cancer Research UK and involves the combination of gemcitabine and MRK003.

A research team from Cambridge found that when these two drugs were combined in animals studies, they had a synergistic effect that enhanced the destruction of pancreatic cancer cells. These promising results prompted a human clinical trial now underway under the auspices of Cancer Research UK’s Drug Development Office and Cambridge University Hospitals Foundation Trust.

How the drug combination seems to work
Gemcitabine is a chemotherapy drug often used in the treatment of pancreatic cancer, bladder cancer, breast cancer, ovarian cancer, and non-small cell lung cancer. It belongs to a drug class called nucleoside analogs (also classified as a pyrimidine analog) and it works by slowing or stopping the growth of cancer cells.

In this latest study, the ability of gemcitabine to kill cancer cells was boosted by the addition of MRK003, an experimental drug in a class called gamma secretase inhibitors. MRK003 blocks a signaling pathway that plays a critical role in providing nourishment to the tumor.

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Following promising results in animal studies, the drug combination is being tested in a clinical trial. According to Professor Duncan Jodrell, head of the clinical trial, “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.”

Other pancreatic cancer treatments under investigation
Jodrell admitted it will be “some time before we’re able to say how successful this will be in patients.” In the meantime, other trials and experiments have been done and are underway. One was a phase I/II trial that involved the combination of gemcitabine and nab-paclitaxel, conducted at Virginia G. Piper Cancer Center Clinical Trials at Scottsdale Healthcare in Arizona.

In that study, the drug combination was associated with a reduction in tumor size in nearly half of the 44 patients, and 48 percent lived for at least one year. The gemcitabine and nab-paclitaxel combination is now being tested in a study involving more than 800 patients.

Investigators are also looking into the benefits of a malaria drug, chloroquine, which has been shown to slow the growth of pancreatic cancer in mice. This discovery has already triggered clinical trials using a similar drug, hydroxychloroquine, in patients who have advanced pancreatic cancer.

Another study has explored yet another drug, gefitinib (Iressa®), an epidermal growth factor receptor tyrosine kinase inhibitor taken orally that was approved by the Food and Drug Administration in May 2003 for treatment of non-small cell lung cancer.

A research team at the Peggy and Charles Stephenson Oklahoma Cancer Center found that administration of gefitinib in the early stages of pancreatic cancer completely eradicated the disease after 41 weeks of treatment. A major problem is diagnosing the disease early; most cases of pancreatic cancer are not discovered until the disease has progressed.

The results of the latest study from Cambridge and Cancer Research UK, as well as other trials, offer promise of improved treatments for pancreatic cancer. For now, it’s not known whether pancreatic cancer cells will be destroyed with a drug combination or researchers will discover other means to stop the disease, but the search continues.

Cancer Research UK
Cook N, Frese KK, Bapiro TE et al. Gamma secretase inhibition promotes hypoxic necrosis in mouse pancreatic ductal adenocarcinoma. Journal of Experimental Medicine 2012. Doi: 10.1084/jem.20111923
National Cancer Institute

Image: Courtesy Wikimedia Commons