Malaria Drug Slows Pancreatic Cancer in Mice

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A malaria drug, chloroquine, has slowed the growth of pancreatic cancer in mice. This discovery by researchers at Dana-Farber Cancer Institute has already prompted clinical trials using hydroxychloroquine, a similar drug, in patients with advanced pancreatic cancer.

Pancreatic cancer has a poor prognosis

Hydroxychloroquine, a form of chloroquine, is an antimalarial drug that has also proved effective in relieving inflammation caused by lupus erythematosus and rheumatoid arthritis. Side effects may include dizziness, headache, hair loss, nausea, and rash. The Food and Drug Administration approved hydroxychloroquine in 1955.

Hydroxychloroquine has an ability to inhibit autophagy, a process by which cells are able to metabolize and eliminate damaged membranes and worn-out proteins. Cancer cells possess a greater ability to conduct autophagy, which they can activate to overcome and survive through chemotherapy.

At Dana-Farber Cancer Institute, a scientific team led by Alec Kimmelman, MD, PhD, a radiation oncologist at Dana-Farber, observed that autophagy was turned on all the time in pancreatic cancer cell lines. This indicated that pancreatic tumors depend on autophagy for their survival, and also that pancreatic cancer could be a good candidate for treatment that inhibits autophagy.

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The research team tested this idea using chloroquine in several different pancreatic cancer cell cultures and three mouse models. The drug “markedly decreased” the growth of pancreatic tumor cells in the cultures.

In the mouse models, one group had human pancreatic cancer cells placed under the skin (xenografts), another had human cells injected into the pancreas, and a third was a genetic model for pancreatic tumors.

In the xenograft mice, all eight untreated mice died of pancreatic cancer within 140 days, but only one of eight mice treated with chloroquine died by 180 days. In the other two treatment groups, chloroquine improved survival by 27 days when compared with untreated mice.

The new clinical trial of hydroxychloroquine will enroll 36 patients with pancreatic cancer who have failed first- or second-line treatments. Results from this study will not be available for at least one year, according to Kimmelman, who is leading the study along with oncologist Brian Wolpin, MD.

Pancreatic cancer is the fourth leading cause of cancer death in the United States. According to the National Cancer Institute, an estimated 43,140 people were diagnosed with the disease in 2010, and 36,800 people died. Prognosis for pancreatic cancer is very poor, with a median survival of less than six months. Use of a malaria drug could someday lead to an improvement.

SOURCE:
Yang S et al. Genes & Development. Published in advance Mar 14, 2011; doi: 10.1101/gad.2016111

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