Brain cancer tumors are resilient to many traditional treatments. Could an intervention to the body's inner clock change this?
Brain and central nervous system (CNS) cancersare aggressive and often resilient to the normal therapies prescribed in these cases, such as chemotherapy and radiotherapy.
The National Cancer Institute of the National Institutes of Health (NIH) estimate that there were around 23,800 new cases of brain and CNS cancers last year, which amounts to 1.4 percent of all new cancer cases.
Following treatment, only 33.6 percent of these people survived for 5 years or longer in the 2007–2013 period.
Over the years, specialists have focused on devising new and much more effective treatments for brain cancer, in an effort to improve the rates of remission and survival.
Now, researchers led by Dr. Satchidananda Panda, from the Salk Institute for Biological Studies in La Jolla, CA, have started to experiment with a new drug that has the potential to disrupt the growth of cancer cells without the toxic side effects of traditional chemotherapy agents.
The researchers studied the effect of a drug called SR9009 on brain tumors in a mouse model. Their findings were published yesterday in the journal Nature.
Experimental drug 'starves' cancer cells
In their study paper, Dr. Panda and colleagues note that the disruption of circadian rhythms — or the internal body clock that regulates our day-to-day biological processes — at cellular level can lead to a higher risk of developing cancer. This, they add, is the case in both humans and mice.
The drug SR9009 acts on a type of protein called REV-ERB, which ensures the correct functioning of circadian rhythms.
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The drug is a "REV-ERB agonist," meaning that it can establish a molecular bond with REV-ERBs, boosting their activity.
The researchers found that the experimental drug leads to the eventual death of cancer cells by impairing their ability to "feed" and grow, which also means that they cannot then replicate and spread further. So, the survival rate of the mice involved in this experiment was increased.
"We've always thought about ways to stop cancer cells from dividing," notes Dr. Panda. "But once they divide, they also have to grow before they can divide again, and to grow they need all these raw materials that are normally in short supply."
"SR9009 is known to cross the blood-brain barrier," the researchers write in their paper, meaning that the drug can be injected into the bloodstream rather than administered directly to the brain.
Another important characteristic of this experimental drug is that, while it appears to be as effective as other compounds used in the treatment of brain cancer, it selectively targeted the cancer cells and did not have a collateral toxic effect.
"[W]hile SR9009 anticancer activity was similar to the current therapeutic standard for glioblastoma [brain cancer], which is temozolomide, SR9009 did not result in toxicity," the researchers write.
Drug 'seemed to work in all types of cancer'
Moreover, the experimental drug's selective cancer cell-targeting properties are not reduced to fighting glioblastoma alone.
In vitro tests showed that SR9009 could be used to effectively attack other types of cancer cell, including those typical to breast cancer, colon cancer, leukemia, and melanoma, or skin cancer.
"Targeting REV-ERBs seemed to work in all the types of cancer we tried. That makes sense because irrespective of where or how a cancer started, all cancer cells need more nutrients and more recycled materials to build new cells."Dr. Satchidananda Panda
This may mean that, in the future, SR9009 could be used to treat a wide array of cancer tumors without the toxic side effects produced by regular chemotherapy drugs.
As Dr. Helen Rippon, chief executive of Worldwide Cancer Research — the charity that co-funded the current study — explains, "Cancer cells often seem to have a broken internal 'clock.' Not only does this disrupt the cells' daily rhythms, but can also turn on molecular circuits that drive tumorgrowth."
"Understanding these underlying faults at the root of cancer is essential," she stresses, "if we are to develop completely new treatments that are more effective and have fewer side effects."
"We are delighted," Dr. Rippon concludes, "that this research is already leading towards new treatments for brain tumors and that early results suggest it could be a fruitful approach for other cancers too."
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