Lab mouse
A nucleoside analog has shown potential for treating primary effusion lymphoma (PEL) and multiple myeloma (MM), according to researchers.
The compound, 6-ethylthioinosine (6-ETI), killed both PEL and MM cells in vitro.
6-ETI also reduced tumor burden and prolonged survival in mouse models of MM and PEL.
Ethel Cesarman, MD, PhD, of Weill Cornell Medicine in New York, New York, and her colleagues conducted this research and disclosed their results in the Journal of Clinical Investigation.
The researchers identified 6-ETI via high-throughput screening, and they initially tested the compound in PEL cell lines. 6-ETI induced necrosis, apoptosis, and autophagy in these cells.
In a xenograft model of PEL, mice treated with 6-ETI experienced “striking and immediate regression of the implanted xenograft within 3 days of treatment,” according to the researchers.
In addition, mice that received 6-ETI had significantly longer progression-free and overall survival than control mice (P<0.0001 for both), and the researchers said there were no obvious toxicities from the treatment.
Looking into the mechanism of 6-ETI, the researchers found that adenosine kinase (ADK) is required to phosphorylate and activate the compound, and PEL cells have high levels of ADK.
Because PEL cells closely resemble plasma cells, the researchers theorized that MM might produce high levels of ADK as well. Experiments in MM cells proved this theory correct.
So the researchers tested 6-ETI in MM cell lines and samples from MM patients. The compound induced apoptosis and autophagy, and it activated a DNA damage response in MM cells.
In a mouse model of MM, 6-ETI treatment significantly reduced tumor burden but did not result in weight loss. And treated mice had significantly longer overall survival than control mice (P<0.005).
Dr Cesarman and her colleagues are now trying to better understand how 6-ETI works and determine what other cancers expressing high levels of ADK might respond to the drug.
“This compound could provide a much-needed approach to treat people with some forms of plasma malignancies as well as other cancers that express ADK,” Dr Cesarman said.
