Simultaneous Inhibition of Two Enzymes Suppresses Growth of Diffuse Large B-cell Lymphoma

Simultaneous blocking of two enzymes has been shown to suppress effectively growth of diffuse large B-cell lymphoma (DLBCL) in a mouse xenograft model and in primary DLBCL cells taken from human patients.

Investigators at the University of Maryland (Baltimore, USA) used a combination of drugs to inhibit the enzymes ERK (extracellular signal-regulated kinase), which acts to regulate cell proliferation and survival, and CHK2 (checkpoint kinase 2), which is involved in responding to cellular DNA damage.

They reported in the July 19, 2011, online edition of the journal Nature Communications that combined inhibition of ERK and CHK2 exerted a potent antitumor effect in a human DLBCL xenograft model and primary DLBCL cells from human patients and may provide a therapeutic advantage. Importantly, the drug combination that inhibited ERK and CHK2 activity did not cause any significant damage to normal cells or tissue.

At the molecular level, the results revealed a positive correlation between ERK and CHK2 expression. ERK physically interacted with CHK2, and inhibition of CHK2 activated ERK.

“The two proteins physically interact, which was not known before, and we may be able to use this interaction for therapeutic advantage,” said senior author Dr. Ronald B. Gartenhaus, associate professor of medicine at the University of Maryland. “We found that treating human B-cell lymphoma cells with both an ERK inhibitor and a CHK2 inhibitor killed substantially more cancer cells than treating the cells with either drug alone. 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.”

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