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

Encouraging oxygen's assault on iron may offer new way to kill lung cancer cells

November 22, 2017
Blocking the action of a key protein frees oxygen to damage iron-dependent proteins in lung and breast cancer cells, slowing their growth and making them easier to kill. This is the implication of a study led by researchers ...

One-size treatment for blood cancer probably doesn't fit all, researchers say

November 22, 2017
Though African-American men are three times more likely to be diagnosed with a blood cancer called multiple myeloma, most scientific research on the disease has been based on people of European descent, according to a study ...

One in four U.S. seniors with cancer has had it before

November 22, 2017
(HealthDay)—For a quarter of American seniors, a cancer diagnosis signals the return of an old foe, new research shows.

Combination immunotherapy targets cancer resistance

November 22, 2017
Cancer immunotherapy drugs have had notable but limited success because in many cases, tumors develop resistance to treatment. But researchers at Yale and Stanford have identified an experimental antibody that overcomes this ...

Researchers discover specific tumor environment that triggers cells to metastasize

November 21, 2017
A team of bioengineers and bioinformaticians at the University of California San Diego have discovered how the environment surrounding a tumor can trigger metastatic behavior in cancer cells. Specifically, when tumor cells ...

New study points the way to therapy for rare cancer that targets the young

November 21, 2017
After years of rigorous research, a team of scientists has identified the genetic engine that drives a rare form of liver cancer. The findings offer prime targets for drugs to treat the usually lethal disease, fibrolamellar ...

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.