New compound targets key mechanism behind lymphoma

April 3, 2012

Scientists at Fox Chase Cancer Center in Philadelphia have come one step closer to developing the first treatment to target a key pathway in lymphoma. The new findings will be announced at the AACR Annual Meeting 2012 on Tuesday, April 3.

"It's an exciting time to be involved in and research," says study author Mitchell Smith, M.D., Ph.D., director of Lymphoma Service at Fox Chase. "There's a new understanding of the disease, and to treat it. I am optimistic that over the next couple of years treatments will continue to get even better and less toxic."

During the study, Smith and his colleagues investigated a compound known as TL32711 (Birinapant), developed by TetraLogic Pharmaceuticals in Malvern, Pennsylvania. The compound works by blocking the process cells used to avoid death, he explains—in other words, it inhibits the process that inhibits cell death. "TL32711 is like a double-negative. It inhibits the inhibitor, and therefore makes cells more sensitive to dying."

To test whether TL32711 works better in some types of lymphomas than others, Smith and his team added it to various lymphoma cells. Since compounds tend to work best when given in combination with other drugs, in some cells they added another compound known as TRAIL, which targets tumor cells.

The researchers found that some types of lymphoma appeared more vulnerable to the effects of TL32711, suggesting these patients should be the first to try the finished product in clinical trials. Specifically, they saw that follicular lymphoma cells and some types of diffuse large B cell lymphomas were more likely to die following treatment. Not surprisingly, adding TRAIL to the mix appeared to make TL32711 even more effective at killing . "We saw the combination worked better than either one alone," says Smith.

Importantly, the researchers saw the cells didn't just die—they died because of the action of the compounds, explains Smith. TL32711 works by enhancing cell death—known formally as apoptosis—and just before cells experience apoptosis, they activate proteins known as caspases. Sure enough, after exposure to the compounds, the level of active caspases increased, confirming the cells were undergoing more apoptosis. "This result confirms that the cells are dying the way they should when you add these compounds," says Smith.

TL32711 is not yet available in the clinic, says Smith, but already some clinical trials are enrolling patients to test its effects. He and his colleagues plan to continue to test the compound in animals, to get a better sense of how it should best be used in humans.

"We're getting a much better understanding of why don't die," he adds. "We're starting to see drugs that hit different pathways in the cell. Our research is about trying to take the compounds that target this particular forward in the most efficient way possible."

Explore further: Researchers discover possible drug targets for common non-Hodgkin's lymphoma

Related Stories

Researchers discover possible drug targets for common non-Hodgkin's lymphoma

July 19, 2011
Researchers at the University of Maryland School of Medicine have discovered a novel interaction between two proteins involved in regulating cell growth that could provide possible new drug targets for treating diffuse large ...

Novel treatment for skin lymphoma

January 17, 2012
Promising findings on a novel combination treatment approach for a chronic type of skin lymphoma are being published today (embargoed for 4 pm) in JAMA's Archives of Dermatology by clinical researchers from Seidman Cancer ...

Recommended for you

Outdoor light at night linked with increased breast cancer risk in women

August 17, 2017
Women who live in areas with higher levels of outdoor light at night may be at higher risk for breast cancer than those living in areas with lower levels, according to a large long-term study from Harvard T.H. Chan School ...

Scientists develop blood test that spots tumor-derived DNA in people with early-stage cancers

August 16, 2017
In a bid to detect cancers early and in a noninvasive way, scientists at the Johns Hopkins Kimmel Cancer Center report they have developed a test that spots tiny amounts of cancer-specific DNA in blood and have used it to ...

Toxic formaldehyde is produced inside our own cells, scientists discover

August 16, 2017
New research has revealed that some of the toxin formaldehyde in our bodies does not come from our environment - it is a by-product of an essential reaction inside our own cells. This could provide new targets for developing ...

Cell cycle-blocking drugs can shrink tumors by enlisting immune system in attack on cancer

August 16, 2017
In the brief time that drugs known as CDK4/6 inhibitors have been approved for the treatment of metastatic breast cancer, doctors have made a startling observation: in certain patients, the drugs—designed to halt cancer ...

Researchers find 'switch' that turns on immune cells' tumor-killing ability

August 16, 2017
Molecular biologists led by Leonid Pobezinsky and his wife and research collaborator Elena Pobezinskaya at the University of Massachusetts Amherst have published results that for the first time show how a microRNA molecule ...

Popular immunotherapy target turns out to have a surprising buddy

August 16, 2017
The majority of current cancer immunotherapies focus on PD-L1. This well studied protein turns out to be controlled by a partner, CMTM6, a previously unexplored molecule that is now suddenly also a potential therapeutic target. ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.