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Malaria drug slows pancreatic cancer growth in mouse models

18 March 2011

A drug routinely prescribed for malaria and rheumatoid arthritis has been shown to shrink or slow the growth of pancreatic tumours in mice.

A drug routinely prescribed for malaria and rheumatoid arthritis has been shown to shrink or slow the growth of pancreatic tumours in mice.

The pre-clinical study results from the Dana-Farber Cancer Institute in Boston, USA, have already prompted a small clinical trial in human patients with advanced pancreatic cancer. The research is published on the Genes and Development journal website.

The oral drug, hydroxychloroquine, is a form of the drug chloroquine, which is used to prevent and treat malaria and is also prescribed for autoimmune diseases, including lupus and rheumatoid arthritis. According to lead researcher, radiation oncologist Alec Kimmelman, it is inexpensive, widely available, and causes relatively mild side effects.

These compounds are of interest in cancer research because they inhibit a process called autophagy that is elevated in cancer cells.

Autophagy, which is also seen at low levels in normal cells, enables cells to break down and eliminate proteins, such as damaged cell membranes and other worn-out parts.  But when nutrients are scarce, cells can digest and feed on these non-essential proteins to avoid starvation.

It is already known that cancer cells are able to activate the autophagy process to help them survive the stress of a variety of cancer treatments, including chemotherapy. But the US team discovered that the process is permanently switched on in pancreatic cell lines, suggesting that pancreatic tumours are highly dependent on autophagy - and therefore excellent candidates for autophagy-inhibiting treatment.

The researchers found that administering chloroquine to cell cultures and testing its effects in three different types of mouse model showed “robust and impressive responses”.

The first Dana-Farber clinical trial of hydroxychloroquine, led by Kimmelman and oncologist Brian Wolpin, MD, will enrol 36 pancreatic cancer patients in whom first- or second-line treatments have failed. The drug will be taken in pill form twice a day. Results won't become available for at least a year, said Kimmelman.

A second, planned clinical trial will combine the drug with radiation in patients with operable pancreatic cancer.

"While these findings are indeed exciting and a cause for optimism, one needs to be mindful that so far the effects, while impressive, have only been shown in mice," said Dr Ronald DePinho, director of the Belfer Institute for Applied Cancer Science at Dana-Farber. "I eagerly await to see how the human studies will progress."

Pancreatic cancers require autophagy for tumor growth
Published in Advance March 15, 2011, doi: 10.1101/gad.2016111 

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