Turning off an enzyme switch that is needed to activate tumor growth may be an effective way to combat an aggressive kind of cancer called T-cell acute lymphoblastic leukemia, according to researchers at New York University's Langone Medical Center.
An investigational drug being developed by GlaxoSmithKline ($GSK) appears to do just this in preclinical studies, acting to halt this fast-spreading cancer in its tracks.
About a quarter of the 500 U.S. adolescents and young adults diagnosed each year with T-cell acute lymphoblastic leukemia don't respond to traditional chemotherapy drugs, so new treatment approaches for the disease are critically needed.
In a study published in the journal Nature, researchers found that the enzyme JMJD3 acts as a cancer "on" switch by splitting off a chemical methyl group of another protein, polycomb repressive complex 2, or PRC2, that helps stop cancer cells from proliferating.
GlaxoSmithKline is already developing an experimental compound called GSKJ4, which is intended to keep this switch off, preventing JMJD3 from destabilizing and dislodging PRC2. When JMJD3 is destabilized and cuts PRC2 loose, this activates the NOTCH1 biological pathway--a common biological process in many cancers. This pathway is especially active in at least half of all people with T-cell acute lymphoblastic leukemia.
"Revealing the actions of JMJD3, and successfully blocking the enzyme to stall tumor progression, shows that new treatments for T-cell acute lymphoblastic leukemia are not simply theoretical, but practical," said senior study investigator and NYU Langone cancer biologist Iannis Aifantis in a statement.
In preclinical studies of mouse models and human cells, researchers found that JMJD3 was highly active in both mouse and human leukemia cells at all stages of tumor growth and development. When the human mouse cells were treated with GSKJ4, JMJD3 activity stopped and all cancer cells eventually died, the researchers report.
Next, NYU Langone researchers are planning to test GSKJ4 against human leukemia cells transplanted into mice as well as in combination with standard chemotherapy in animals with leukemia.