Potential treatment for deadly HIV-related blood cancer

Researchers have discovered a promising new way to treat a rare and aggressive blood cancer that is most commonly found in people infected with HIV. A class of drugs called bromodomain and extra- terminal (BET) inhibitors effectively targets primary effusion lymphoma (PEL), which is a type of cancer for which those drugs were not expected to be effective.

“It's a reversal of the paradigm,” said principal investigator Preet Chaudhary, MD, PhD, chief of the Nohl Division of Hematology and Blood Diseases at the Keck School of Medicine of University of Southern California in Los Angeles. “Our results suggest that this new class of drug may be an effective treatment for a wider range of cancers than previously thought.”

PEL is caused by infection with Kaposi's sarcoma-associated herpes virus, which is the most common cause of cancer among patients with AIDS. The prognosis for PEL is poor, with a median survival of 3 to 6 months. Thus, there is a critical need for new therapies for the disease.

Chaudhary and his colleagues show that inhibitors targeting the BRD4 protein blocked growth of PEL cells in a test tube and in a mouse model. The results were surprising, because BET inhibitors were thought to be only effective against cancers linked to an overexpression of the Myc gene.

“We actually found that cancers that overexpress Myc are not as responsive to BRD4 inhibitors. PEL is more responsive,” Chaudhary said. The study was published in Oncogene (2013; doi: 10.1038/onc.2013.242).

Cancers like multiple myeloma and Burkitt's lymphoma overexpress the Myc gene and have been shown to respond to BRD4 inhibitors. In PEL, the Myc gene is moderately expressed and there is no chromosomal translocation as is seen in multiple myeloma or Burkitt's.

More research is needed to create compounds ready for testing in people. Once those drugs are ready for clinical trial, data from this study suggest that they may treat a wide range of cancers. Chaudhary anticipates testing them alone and in combination with other drugs.
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