A lymphoma driver called BCL6 suppresses the expression of cell death genes. A new molecule designed at Stanford Medicine blocks its activity and activates downstream genes to trigger cell death.

A two-headed molecule designed by Stanford Medicine researchers hijacks one of the most common protein drivers of B-cell lymphoma, flipping it from its role as a promoter of cell growth into an arbiter of cell death. In mice, a short course of twice-a-day treatment eliminated aggressive lymphoma tumors within 11 days.

The approach builds on a strategy the researchers have been refining for several years: Rather than trying to block a cancer-causing protein, they engineer a small molecule that physically links the culprit with another molecule that switches on the cell’s own self-destruct program. A similar approach may work for other types of cancers and autoimmune diseases, the researchers believe.

“We’re trying to essentially fight cancer with its cause — taking the driving force of the cancer and then rewiring it to activate cell death mechanisms,” said Gerald Crabtree, MD, the David Korn, MD, Professor in Pathology and a professor of developmental biology.

Crabtree shares senior authorship of the study, which was published online July 20 in Cell, with Nathanael Gray, PhD, the Krishnan-Shah Family Professor and a professor of chemical and systems biology; Stephen Hinshaw, PhD, assistant professor of molecular and cellular physiology; and Michael Green, PhD, director of translational and laboratory research, lymphoma/myeloma at the MD Anderson Cancer Center. Graduate student Meredith Nix and postdoctoral scholar Sai Gourisankar, PhD, are the lead authors of the research.

https://www.sciencedirect.com/science/article/abs/pii/S0092867426007579?fr=RR-2&ref=pdf_download&rr=a2d279fc0e9c25c3