Many health experts view immunotherapy as the most promising broad approach for curing cancers. Within the broad immunotherapy approach there are many sub-approaches–distinct approaches on how to activate the immune system against cancer. The article quoted below discusses a new sub-approach.
(p. D4) Within every cancer are molecules that spur deadly, uncontrollable growth. What if scientists could hook those molecules to others that make cells self-destruct? Could the very drivers of a cancer’s survival instead activate the program for its destruction?
That idea came as an epiphany to Dr. Gerald Crabtree, a developmental biologist at Stanford, some years ago during a walk through the redwoods near his home in the Santa Cruz mountains.
“I ran home,” he said, excited by the idea and planning ways to make it work.
Now, in a paper published Wednesday [July 26, 2023] in the journal Nature, Dr. Crabtree, a founder of Shenandoah Therapeutics, which is developing cancer drugs, along with Nathanael S. Gray, a professor of chemical and systems biology at Stanford, and their colleagues report that they have done what he imagined on that walk. While the concept is a long way from a drug that could be given to cancer patients, it could be a target for drug developers in the future.
. . .
In laboratory experiments with cells from a blood cancer, diffuse large B-cell lymphoma, the researchers designed and built molecules that hooked together two proteins: BCL6, a mutated protein that the cancer relies on to aggressively grow and survive, and a normal cell protein that switches on any genes it gets near.
. . .
BCL6, at one end of the dumbbell, guides the molecule toward cell-death genes that are part of every cell’s DNA and are used to get rid of cells that are no longer needed.
. . .
When the dumbbell, guided by BCL6, gets near the cell-death genes, the normal protein on the end of the dumbbell arms those death genes. Unlike other processes in the cell that can be reversed, turning on cell-death genes is irreversible.
. . .
The concept could potentially work for half of all cancers, which have known mutations that result in proteins that drive growth, Dr. Crabtree said. And because the treatment relies on the mutated proteins produced by the cancer cells, it could be extremely specific, sparing healthy cells.
For the full story see:
(Note: ellipses, and bracketed date, added.)
(Note: the online version of the story was updated July 31, 2023 [sic], and has the title “Flipping a Switch and Making Cancers Self-Destruct.” Where the wording of the versions differs, the passages quoted above follow the online version.)
The academic article co-authored by Crabtree in Nature (published in July with an “issue date” of Aug. 10) and mentioned above is: