Invention of a strange molecule that causes cancer cells to destroy themselves

A team at Stanford has invented a strange new molecule that could lead to drugs that turn on genes and cause cancers to fight themselves.

Every cancer contains molecules that promote uncontrolled growth. What if scientists could link those molecules to others that cause self-destruction in cells? Can the forces that promote cancer survival trigger its destruction?

This idea came to Dr. Gerald Crabtree, a developmental biologist at Stanford, during a walk in the red forest near his home and he immediately began implementing this idea and planning to transform it. it comes true.

In a recent study published in the journal Nature, Dr. Crabtree, along with Nathanael S. Gray, a professor of systems biology and chemistry at Stanford, and several colleagues in the group, reported the results they achieved. was from Dr. Crabtree's idea. Although developing a drug based on this concept is still far off, it has the potential to be a target for future drug developers.

Jason Gestwicki, professor of medicinal chemistry at the University of California, San Francisco, describes the idea as brilliant and compares it to turning an essential vitamin into a poison that causes cancer cell death: " It's brilliant. It turns something the cancer cell needs to survive into something that can kill it, like turning your vitamins into poison. '

Dr. Louis Staudt, director of the Cancer Genome Center at the National Cancer Institute, calls this a potential new approach to turning cancer against itself . He expressed interest in conducting clinical trials with patients who have exhausted other treatment options once this treatment is further developed.

For their laboratory experiments using cells from a blood cancer called diffuse large B-cell lymphoma , the researchers devised molecules that link two proteins together: BCL6 , a mutant protein that cancer depends on to thrive and survive , and a normal protein that activates neighboring genes.

This new approach could be an improvement on the challenging task of blocking all BCL6 molecules with drugs. By rewinding only part of the BCL6 molecules, it can kill cancer cells.

Dr. Crabtree believes this concept could work for half of all cancers, because they involve known mutations that create growth-promoting proteins. Additionally, because the treatment targets cancer cell-specific mutant proteins, it can be highly targeted and spared healthy cells.

Dr. Crabtree explained two important discoveries that made this work possible. The first is to identify "driver genes" - about a few hundred genes that, when mutated, contribute to the spread of cancer. The second was the discovery of the cell death pathway, which is used to eliminate bad cells. Each individual has approximately 60 billion cells that are affected daily by these pathways.

According to Dr. Staudt, BCL6 is a key regulator of these cancer cells. When its function is completely disrupted, the cell loses its identity and realizes that something is seriously wrong.

BCL6, a mutant protein that cancer depends on to grow.

The main effect of the experimental treatment, as Dr. Crabtree explains, is to activate genes that cause cell death . The team tested the hybrid molecule on mice, however, as Dr. Staudt pointed out, humans are biologically very different from mice.

Stuart L. Schreiber, professor of chemistry and chemical biology at Harvard and a previous collaborator of Dr. Crabtree described the work as "exciting" but cautioned that it is not yet a drug and remains a long way ahead.