Targeting lymphoma's command center

Non-Hodgkin’s Lymphoma is the seventh most common type of cancer in the United States. Some forms of the disease respond well to treatment, others are more stubborn and aggressive.

But now, a new discovery may change the way doctors treat the most difficult cases they encounter by targeting the cancer like a gamer targets and kills in a video game.

"Cancer cells are machines, and as we learn how they work, then we can learn how to block their functions," says Dr. Ari Melnick, Professor of Medicine at Weill Cornell Medical College.

Patients with aggressive forms of Non-Hodgkin’s Lymphoma have too much of the protein Malt-One, which tells cancer cells to grow and survive.
"It basically is the crutch they use to walk on" says Dr. Melnick.

Doctors have recently discovered that a new compound known as MI-2 activates Malt-One and kills it, like hitting and destroying a control center.

MI-2 was tested in animals and human samples of lymphoma, researchers found the agent didn’t pose any toxicity, which suggests it may be a gentler alternative treatment to standard chemotherapy.

Jane Sarnoff just finished the standard treatment for her Non-Hodgkin’s Lymphoma, a regimen that included four chemo drugs used in conjunction with other agents.

“It’s really nasty,” said Sarnoff, who feels alternatives to chemo are greatly needed.

Jane is now in remission and hopes this new discovery will help others like her in the future undergo treatment.

If Malt-One is successful in trials, the drug therapy could possibly help other forms of lymphoma, inflammatory and autoimmune disorders.

BACKGROUND: Lymphoma is the most common blood cancer. The two main forms are Hodgkin lymphoma and non-Hodgkin lymphoma. Lymphoma occurs when white blood cells, lymphocytes, grow abnormally. The body has two main type of lymphocytes that can develop into lymphomas, B-lymphocytes (B-cells) and T-lymphocytes (T-cells). The cancerous lymphocytes can travel to any different parts of the body, including the lymph nodes, bone marrow, spleen, blood, other organs, and can form tumors. Non-Hodgkin lymphoma (NHL) is the most common lymphoma cancer. Incidence rates for NHL have almost doubled since the 1970s. Of the 500,000 Americans who have lymphoma, around 332,000 have NHL. NHL is not a single disease. It is a group of several closely related cancers. The World Health Organization estimates 61 different types of NHL. (Source: www.lymphoma.org)

SYMPTOMS: Common symptoms of NHL include swelling of the lymph nodes, fever, night sweats, lack of energy, and unexplained weight loss. The causes of NHL are unknown, but risks include: a family history, affected with an autoimmune disease, have received an organ transplant, have been infected with viruses like AIDS or Hepatitis C, or have been exposed to chemicals like pesticides. (Source: www.lymphoma.org)

STAGES: NHL is divided into four stages:
Stage I (early disease): The cancer is only in one lymph node, in one organ, or in an area outside the lymph node.
Stage II (locally advanced disease): The cancer is found in two or more lymph node regions on one side of the diaphragm.
Stage III (advanced disease): The cancer involves lymph nodes above and below the diaphragm.
Stage IV (widespread disease): The cancer is found in several parts of one or more organs or tissues (in addition to the lymph nodes), in the liver, blood, or bone marrow. (Source: www.lymphoma.org)

NEW TECHNOLOGY: Treatment options can include: watchful waiting, radiation therapy, novel targeted agents, stem cell transplantation, or chemotherapy. However, there is a certain subtype of Non-Hodgkin's lymphoma that is resistant to chemotherapy, called activated B-cell-DLBCL (diffuse large B-cell lymphoma). An international effort discovered the experimental molecule agent, MI-2, that inactivates the key protein that is responsible for the growth and survival of activated B-cell-DLBCL, known as MALT1. Researchers say that a single drug cannot cure lymphoma, which is why they need to combine agents that can kill the different cellular pathways that lymphoma cells use to survive. They believe that the use of chemotherapy is too toxic and needs to be eliminated in treating lymphoma and the discovery of MI-2 will bring them closer to creating a combination of molecular targeted therapy regimens. MALT1 is the only paracaspase that is produced in humans and it is a particular protein that can rip apart other proteins. So, when MALT1 cuts proteins in activated B-cell-DLBCLs, it can activate growth and can stop other proteins from inhibiting that growth. When the researchers tested MI-2 in mice, they found that it had stopped the growth of cancer and did it without toxicity in normal tissues. Researchers believe that if MI-2 is successful in human clinical trials, then it could play a role in other diseases, including MALT1 lymphoma (a lower-grade type of lymphoma). It could also be beneficial for a variety of inflammatory and autoimmune diseases. (Source: http://weill.cornell.edu/news/releases/wcmc/wcmc_2012/12_10_12-2.shtml)

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FOR MORE INFORMATION, PLEASE CONTACT:

Lauren Woods
Senior Media Associate
Weill Cornell Medical College
(646) 317-7401
Law2014@med.cornell.edu

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