Researchers at Stanford are developing a molecule that forces cancer cells to kill themselves

In context: Every day, billions of cells in the human body die due to a natural process known as apoptosis. When apoptosis does not work as designed, cells become cancerous and can cause life-threatening disease. Now researchers at Stanford University are working on a new way to treat a specific type of cancer and possibly kill it for good.

The researchers’ recently published study describes a way to reactivate apoptosis in mutated cells, which would amount to forcing the cancer to self-destruct using a bioengineered, binding molecule.

Gerald Crabtree, one of the study’s authors and a professor of developmental biology, said he came up with the idea while hiking in Kings Mountain, California, during the pandemic period. The new compound should bind two proteins already present in the cancer cells, turning apoptosis back on and causing the cancer to kill itself.

“We want to essentially have the same kind of specificity that can eliminate 60 billion cells without bystanders,” Crabtree said, so that no cell is destroyed if it is not the right target of this new killing mechanism. The two proteins in question are known as BCL6, an oncogene that suppresses apoptosis-promoting genes in B-cell lymphoma, and CDK9, an enzyme that catalyzes gene activation instead.

Mutated BCL6 proteins block a signal that should normally prompt cancer cells to activate apoptosis. Traditional, non-destructive cancer treatments target oncogenes to try to stop the cancer, while the new study proposes a mechanism to exploit them instead. “You take something that the cancer is addicted to in order to survive and you flip the script and make that the very thing that kills the cancer,” Crabtree said.

The researchers tested the new molecule designed to bind BCL6 and CDK9 in diffuse large B-cell lymphoma cells in a laboratory setting, where the compound was found to be effective at killing the cancer cells. They then tested the compound in healthy mice to see if it had a toxic effect on normal cells, which it did not. However, the molecule appeared to target a specific type of immune cells (B cells) that also contain a non-mutated version of the BCL6 protein.

The team is now testing the molecule on mice affected by diffuse large B-cell lymphomas, to see if the method is effective in killing cancer in living animals. The technique relies on the natural supply of BCL6 and CDK9 in cells, meaning it will likely only work on cancerous lymphomas. After testing the new molecule with 859 different types of cancer cells in the laboratory, the researchers confirmed that it could only kill diffuse large B-cell lymphoma cells.