New research has identified a potential treatment for a rare but previously incurable form of lymphoma that is observed primarily in patients with HIV/AIDS infection.
A class of drugs already approved by the FDA was found to treat this disease, primary effusion lymphoma (PEL). This study, done in vitro and in animal models, was published in Oncogene (2015; doi:10.1038/onc.2015.245).
These immunomodulatory drugs, or IMiDs, were actually more effective on PEL than they have been on the cancer for which they were approved, multiple myeloma.
“That was the ‘ah ha’ moment,” said Preet Chaudhary, MD, PhD, chief of the Jane Anne Nohl Division of Hematology and Center for the Study of Blood Diseases at the Keck School of Medicine of the University of Southern California (USC).
“We have this disease for which there is no cure available, and these cancer cells are being selectively killed by this drug. So then we decided to pursue it further.”
The further study yielded an understanding of the mechanism of action by which the drugs work against PEL. That knowledge led lead author Ramakrishnan Gopalakrishnan, PhD, a USC research associate, to discover that IMiDs display synergistic anti-PEL effects when combined with another new class of drugs, called BRD4 inhibitors.
“There were already five clinical trials going on for BRD4 inhibitors related to other cancers,” Gopalakrishnan said in explaining the decision process in the USC research. “So, when we combined the drugs, we knew how they could be toxic to this other situation with PEL.”
“Not only have we figured out that the drug works,” Chaudhary explained, “but [Gopalakrishnan] has also figured out what the underlying molecular mechanism is. And that has allowed us to combine this drug with other drugs in a more intelligent way. “
Chaudhary’s lab has done previous work on cancers that are found in patients with human immunodeficiency virus (HIV) infection, including cancers such as PEL that are caused by infection with Kaposi’s sarcoma associated herpesvirus, also known as Human Herpesvirus-8.
“Primary effusion lymphoma is very aggressive. Median survival with current therapy is just three to six months,” Chaudhary noted.
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“And the current treatment is also very toxic and requires medications that have other side effects and that need to be given intravenously. This becomes an issue for countries with limited resources, for example in Africa where this disease is prevalent.”
The study results are promising, but Chaudhary cautioned that the research is based on in vitro and animal model studies that involved putting human lymphoma cells into immunodeficient mice.
“We are not suggesting that the patients begin taking these drugs,” Chaudhary said, “But the results do provide a very strong rationale for the clinical testing of these drugs.”
Because the medicines are all FDA-approved, a clinical trial could occur quickly, the researchers believe.