Stanford scientists turn a cancer driver into a kill switch

A Stanford-designed molecule turns a major lymphoma-promoting protein against cancer cells, activating their own self-destruct machinery instead of simply blocking tumor growth. In mice, the treatment completely eliminated aggressive human lymphoma tumors within 11 days, although much more testing is needed before it could reach patients. Stanford Medicine researchers have developed a two-part molecule that turns a major driver of B-cell lymphoma against the cancer cells that depend on it. In mice, twice-daily treatment with the experimental compound caused aggressive lymphoma tumors to disappear within 11 days. The work advances a strategy the research team has been developing for years. Instead of simply shutting down a cancer-promoting protein, the scientists designed a small molecule that connects it to another protein capable of activating the cell's built-in death program.

The researchers believe this type of molecular rewiring could eventually have applications beyond lymphoma, including other cancers and some autoimmune diseases. "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 in Cell, with Nathanael Gray, PhD, the Krishnan-Shah Family Professor and a professor