Researchers have uncovered a new way to attack lymphoma by targeting a non-catalytic region of a key regulatory enzyme, rather than its traditional active site.
Researchers at VCU Massey Comprehensive Cancer Center found a surprising new angle for fighting lymphoma using a medication that is already approved for abnormal heart rhythms.
Instead of treating cancer cells with a broad toxic hit, the approach aims at a specific set of enzyme functions that lymphoma cells rely on. In tests, the strategy wiped out cancer cells and slowed tumor growth with little to no toxicity. The work, reported in Pharmacological Research, points to a new direction for precision medicine in cancer by focusing on a part of the target that most drug programs have ignored.
“These findings redefine our understanding of the USP11 enzyme and shed light on the anti-tumor effects of RBF4—an existing heart medication—illuminating a new therapeutic approach in lymphoid malignancies and beyond,” said study senior author Ronald Gartenhaus, M.D., associate director for veterans health at Massey and director of the Richmond VA Cancer Center.
Rethinking How to Target Cancer Enzymes
USP11 is part of the deubiquitinase family, or (DUB), a class of enzymes that help control protein stability inside cells. You can think of this system as cellular quality control. Proteins are constantly being tagged, untagged, and routed for reuse or breakdown, and DUB enzymes help remove those tags to keep the balance. Because cancer cells are unusually dependent on these protein control circuits, DUBs have long looked like appealing targets.
