Roswell Park Researchers Clarify Mechanisms Of Novel Therapy In Non-Hodgkin's Lymphoma Cells

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Roswell Park Researchers Clarify Mechanisms Of Novel Therapy In Non-Hodgkin's

Lymphoma Cells

09 Dec 2008

A significant number of patients with non-Hodgkin's lymphoma have poor clinical

outcomes because their cancer cells have become resistant to immunochemotherapy.

Scientists at Roswell Park Cancer Institute hope to improve those outcomes by

identifying the pathways that lymphoma cells develop to evade immunochemotherapy

- and by developing novel therapeutic strategies to shut those pathways down.

Obatoclax, a novel targeted cancer therapy , is capable of inducing two forms of

cell death in B cell non-Hodgkin's lymphoma (B-NHL) cells and appears to have

the potential to overcome acquired resistance to chemotherapeutic agents,

according to a study conducted by Francisco J. -Ilizaliturri, MD,

Departments of Medicine and Immunology, RPCI. The research will be presented at

the 2008 annual meeting of the American Society of Hematology, December 6-9, San

Francisco, CA.

B cell non-Hodgkin's lymphoma, a cancer of the cells of the lymph system, makes

up about 85% of NHL cases diagnosed in the United States. The Bcl-2 family is a

group of proteins known to affect patient outcomes and is involved in

development, sustaining and progression of various subtypes of NHL. Dr.

-Ilizaliturri and colleagues examined the molecular mechanisms of

Obatoclax, a targeted therapy, which is designed to inhibit several members of

the Bcl-2 protein family.

Studies were conducted in various rituximab-chemotherapy-sensitive or resistant

B-cell lymphoma cell lines and in tumor cells isolated from 25 patients with

different subtypes of B cell lymphomas and Hodgkin's disease.

Dr -Ilizaliturri and his group of investigators demonstrated that

Obatoclax is a potent inhibitor of Bcl-2 family proteins, has significant

anti-tumor activity against various rituximab-chemotherapy-sensitive or

-resistant lymphoma cell lines, as well as in malignant B-cells derived from

patients with diffuse large B cell lymphomas (DLBCL). In addition, they found

that Obatoclax can enhance the biological activity of rituximab in vitro and

sensitize NHL cells to the cytotoxic effects of a wide spectrum of chemotherapy

agents. Scientist observed several signal events in NHL cells exposed to

Obataclox, suggesting that this novel compound has a dual mechanism of action

and is capable of inducing cell death (apoptosis) and/or cell self-degradation

(autophagy) in B-NHL cell lines and can potentially be utilized to characterize

shared pathways that regulate apoptosis, autophagy and possible necrosis within

a given lymphomatous tumor.

" As this class of agents moves forward in the treatment of hematological

malignancies, the clinical optimization of Obatoclax and its incorporation into

already available rituximab-chemotherapy regimens will likely be the result of

translational research aimed at characterizing the molecular apoptotic and

non-apoptotic (autophagy) pathways responsible for its anti-tumor activity " said

Dr. -Ilizaliturri.

Roswell Park Cancer Institute, founded in 1898, is the nation's first cancer

research, treatment and education center. The Institute was one of the first

cancer centers in the country to be named a National Cancer Institute-designated

comprehensive cancer center and remains the only facility with this designation

in Upstate New York. RPCI is a member of the prestigious National Comprehensive

Cancer Network, an alliance of the nation's leading cancer centers; maintains

affiliate sites; and is a partner in national and international collaborative

programs.

Roswell Park Cancer Institute

Article URL: http://www.medicalnewstoday.com/articles/132318.php