What if cancer cells became their own enemies? A team from Stanford seems to have found a way to achieve this goal.
In our bodies, billions of cells are destroyed daily thanks to a process called apoptosis. This biological mechanism eliminates unnecessary or damaged cells to maintain balance. However, cancer cells escape this rule and proliferate endlessly.
Stanford researchers have designed an innovative molecule capable of changing the game. Using a "molecular glue," they combined two proteins, BCL6 and CDK9, which normally act independently. This unexpected duo forces cancer cells to activate their own self-destructive genes.
BCL6, a protein often involved in lymphomas, usually deactivates apoptosis-related genes, granting diseased cells a kind of immortality. But once linked to CDK9, this very protein becomes their downfall by reactivating these genes and triggering cell death.
The original idea came from Gerald Crabtree, a developmental biologist. Fascinated by apoptosis and its key role in cell survival, he envisioned a reversed approach: turning a vital dependency of cancer cells into a lethal signal.
The laboratory results are promising. The molecule demonstrated remarkable effectiveness against diffuse large B-cell lymphoma (a blood cancer) without affecting healthy cells. Tests on 859 different cancer cell lines revealed exceptional specificity: only lymphoma cells were killed.
Even better, experiments on healthy mice showed no notable side effects. More specifically, scientists observed that the molecule also killed a specific category of healthy B cells in the animals (a type of immune cell), but without major impact. Thus, unlike conventional treatments like chemotherapy, this method spares non-cancerous cells while effectively eliminating diseased ones.
The researchers hope this approach will bypass resistance, a significant challenge for traditional targeted therapies. By simultaneously activating multiple apoptosis signals, cancer could be overwhelmed before it has a chance to adapt.
The next steps include testing on mice affected by lymphoma and developing similar molecules for other oncogenes. If successful, this "molecular glue" could become a revolutionary weapon in the fight against cancer.
What is apoptosis?
Apoptosis is a fundamental biological process whereby the cells in our body program their own destruction. Unlike necrosis, which is an accidental form of cell death often associated with inflammation, apoptosis is a controlled, clean, and silent mechanism.
This phenomenon is essential for maintaining balance in the human body. Every day, about 60 billion cells are eliminated, particularly in rapidly renewing tissues such as blood or the intestines. This renewal helps maintain organ health and remove defective cells.
In cancers, this process often fails. Cancer cells manage to deactivate apoptosis signals, allowing them to survive indefinitely. Understanding and reactivating this mechanism therefore represents a significant step forward in developing anticancer therapies.
Apoptosis also plays an important role in embryonic development and immunity, for example, by eliminating potentially autoimmune cells before they can become harmful.
Article author: Cédric DEPOND