The first step to finding a new treatment for cancer is to identify pivotal factors, such as genes, that the disease cannot survive without. For the majority of B cell lymphomas, Dr Melnick and colleagues in New York have discovered one such gene: EZH2.
EZH2 is a master gene regulator used by B cells- the immune cells in charge of making antibodies. Master regulators like EZH2 simultaneously switch many genes on or off, and by doing so they coordinate the actions of multiple genes to achieve a common function. In the case of EZH2, this is the promotion of the division of B cells.
In normal B cells, EZH2 is only active during an immune response against invading foreign microbes, where many fully-fledged antibody producing B cells are needed.
However, this ability of EZH2 to drive division also means that it is utilized by the majority of lymphoma cells to promote their accelerated division. In addition, EZH2 often cooperates with another gene, the survival-promoting BCL2, to enable lymphomas to thrive further.
As the majority of B cell lymphomas depend on these genes for the vital functions of growth and survival, blocking the activity of both genes simultaneously will cripple the disease on both fronts.
This combined approach therefore constitutes a potentially powerful treatment. Accordingly, the EZH2 and BCL2 inhibitors had a much stronger effect when applied together than individually in tests on cells and mouse models. This research has provided a strong foundation for the further development of this therapeutic approach against B cell lymphomas.
Written by Betty Lau.