Researchers Discover Possible Drug Targets For Common Non-Hodgkin's Lymphoma

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BlankResearchers Discover Possible Drug Targets For Common Non-Hodgkin's

Lymphoma

20 Jul 2011

Researchers at the University of land 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 B-cell

lymphoma, the most common type of non-Hodgkin's lymphoma.

In a study published online in Nature Communications, the scientists report that

they have found a complex molecular and functional relationship between ERK

(extracellular signal-regulated kinase), a protein that helps to regulate cell

proliferation and survival, and CHK2 (checkpoint kinase 2), a protein that is

involved in the cellular DNA damage response. They also demonstrated, for the

first time, elevated levels of both proteins in diffuse large B-cell lymphoma

cells, compared to non-cancerous cells.

B. Gartenhaus, M.D., associate professor of medicine at the University of

land School of Medicine and the senior author, says researchers found that

CHK2 appears to regulate the activity of ERK, although the exact mechanism is

not clear. " The two proteins physically interact, which was not known before,

and we may be able to use this interaction for therapeutic advantage. We found

that treating human B-cell lymphoma cells with both an ERK inhibitor inhibitor

and a CHK2 inhibitor killed substantially more cancer cells than treating the

cells with either drug alone, " he says.

" Based on our findings, we believe that a combination therapy targeting both ERK

and CHK2 could offer a potential new approach to treating diffuse large B-cell

lymphoma, " says Dr. Gartenhaus, who is co-leader of the Program in Molecular and

Structural Biology at the University of land and Greenebaum

Cancer Center.

The drugs used to inhibit ERK and CHK2 caused the cancer cells to die through a

process called apoptosis, or programmed cell death. Human cells normally

self-destruct in a controlled manner, but cancer cells lose this ability and

consequently grow uncontrollably.

E. Albert Reece, M.D., Ph.D., M.B.A., vice president of medical affairs at the

University of land and dean of the University of land School of

Medicine, says, " This is a very important discovery that may ultimately benefit

patients with diffuse large B-cell lymphoma, a common hematological malignancy

that can be difficult to treat. These findings provide valuable new insight into

the molecular make-up of this cancer that may lead to new targeted drug

therapies. "

Lymphoma is a cancer that originates in the lymphocytes (a type of white blood

cell) of the immune system. Diffuse large B-cell lymphoma is a fast-growing,

aggressive form of non-Hodgkin's lymphoma. It accounts for about 30 to 35

percent of all non-Hodgkin's lymphomas, and about 25,000 new cases are diagnosed

each year. Non-Hodgkin's lymphomas usually are treated with several types of

chemotherapy cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP)

and a biological therapy, such as the monoclonal antibody rituximab (Rituxan).

Radiation therapy may be used on occasion, and bone marrow or stem cell

transplantation may also be a treatment option.

Dr. Gartenhaus says researchers hope the study findings will help to develop new

therapies that will be effective and well-tolerated by patients. " We believe it

is important to identify drugs that can improve the efficacy and reduce the

toxicity of standard anti-lymphoma therapy, " he says.

The new research showed that using compounds to inhibit ERK and CHK2 did not

cause any significant damage to normal cells or tissue examined in the lab,

according to Bojie Dai, Ph.D., a postdoctoral fellow at the University of

land School of Medicine and the lead author. " We hope that new therapies

directed at these two proteins would have modest side effects because they would

target only the lymphoma cells, " Dr. Dai says.

Dr. Gartenhaus says that researchers don't know yet whether the interaction

between ERK and CHK2 occurs in other types of lymphoma.

The study was funded by a grant from the National Institutes of Health and a

Merit Review Award from the U.S. Department of Veterans Affairs.

Source: University of land Medical Center

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Article URL: http://www.medicalnewstoday.com/releases/231398.php