Researchers Develop New Method That Tricks Cancer Cells Into Killing Themselves (stanford.edu) 21
Our bodies divest themselves of 60 billion cells every day through a natural process called "apoptosis". So Stanford medicine researchers are developing a new approach to cancer therapy that could "trick cancer cells into disposing of themselves," according to announcement from Stanford's medical school:
Their method accomplishes this by artificially bringing together two proteins in such a way that the new compound switches on a set of cell death genes... One of these proteins, BCL6, when mutated, drives the blood cancer known as diffuse large cell B-cell lymphoma... [It] sits on DNA near apoptosis-promoting genes and keeps them switched off, helping the cancer cells retain their signature immortality.
The researchers developed a molecule that tethers BCL6 to a protein known as CDK9, which acts as an enzyme that catalyzes gene activation, in this case, switching on the set of apoptosis genes that BCL6 normally keeps off. "The idea is, Can you turn a cancer dependency into a cancer-killing signal?" asked Nathanael Gray, PhD, co-senior author with Crabtree, the Krishnan-Shah Family Professor and a chemical and systems biology professor. "You take something that the cancer is addicted to for its survival and you flip the script and make that be the very thing that kills it...."
When the team tested the molecule in diffuse large cell B-cell lymphoma cells in the lab, they found that it indeed killed the cancer cells with high potency. They also tested the molecule in healthy mice and found no obvious toxic side effects, even though the molecule killed off a specific category of of the animals' healthy B cells, a kind of immune cell, which also depend on BCL6. They're now testing the compound in mice with diffuse large B-cell lymphoma to gauge its ability to kill cancer in a living animal. Because the technique relies on the cells' natural supply of BCL6 and CDK9 proteins, it seems to be very specific for the lymphoma cells — the BCL6 protein is found only in this kind of lymphoma cell and in one specific kind of B cell. The researchers tested the molecule in 859 different kinds of cancer cells in the lab; the chimeric compound killed only diffuse large cell B-cell lymphoma cells.
Scientists have been trying to shut down cancer-driving proteins, one of the researchers says, but instead, "we're trying to use them to turn signaling on that, we hope, will prove beneficial for treatment."
The two researchers have co-founded the biotech startup Shenandoah Therapeutics, which "aims to further test this molecule and a similar, previously developed molecule," according to the article, "in hopes of gathering enough pre-clinical data to support launching clinical trials of the compounds.
"They also plan to build similar molecules that could target other cancer-driving proteins..."
The researchers developed a molecule that tethers BCL6 to a protein known as CDK9, which acts as an enzyme that catalyzes gene activation, in this case, switching on the set of apoptosis genes that BCL6 normally keeps off. "The idea is, Can you turn a cancer dependency into a cancer-killing signal?" asked Nathanael Gray, PhD, co-senior author with Crabtree, the Krishnan-Shah Family Professor and a chemical and systems biology professor. "You take something that the cancer is addicted to for its survival and you flip the script and make that be the very thing that kills it...."
When the team tested the molecule in diffuse large cell B-cell lymphoma cells in the lab, they found that it indeed killed the cancer cells with high potency. They also tested the molecule in healthy mice and found no obvious toxic side effects, even though the molecule killed off a specific category of of the animals' healthy B cells, a kind of immune cell, which also depend on BCL6. They're now testing the compound in mice with diffuse large B-cell lymphoma to gauge its ability to kill cancer in a living animal. Because the technique relies on the cells' natural supply of BCL6 and CDK9 proteins, it seems to be very specific for the lymphoma cells — the BCL6 protein is found only in this kind of lymphoma cell and in one specific kind of B cell. The researchers tested the molecule in 859 different kinds of cancer cells in the lab; the chimeric compound killed only diffuse large cell B-cell lymphoma cells.
Scientists have been trying to shut down cancer-driving proteins, one of the researchers says, but instead, "we're trying to use them to turn signaling on that, we hope, will prove beneficial for treatment."
The two researchers have co-founded the biotech startup Shenandoah Therapeutics, which "aims to further test this molecule and a similar, previously developed molecule," according to the article, "in hopes of gathering enough pre-clinical data to support launching clinical trials of the compounds.
"They also plan to build similar molecules that could target other cancer-driving proteins..."
Disrupting cancer pathways (Score:5, Insightful)
Re-enabling that pathway (or signaling it in other ways) seems like a promising approach with high effectiveness, and much lower downsides than chemo or radiation.
The problem with it is that developing such therapies is still very difficult. They have found something that works with one particular type of cancer, and great; but there are a lot of types of cancer.
Re:Disrupting cancer pathways (Score:4, Interesting)
Note, I have seen hundreds of things that work in cells in a lab and then totally failed in animal model (if lucky) .. if unlucky it fails in late clinical trials or worse after approval. The problem with any small molecule that binds to proteins is usually side effects. That is, the drug may be found to bind to and fuck up other proteins or molecules including those important to mechanisms of normal healthy cells. Second, they can be mutated around by the cancer cell. By that I mean the tumor will have cancer cells with a mutant form of the target proteins (BCL6 or CDK9) such that the drug doesn't bind, or, there will be a population of cells that happen to have efflux mechanisms that bind to the drug. Note there are other mechanisms of resistance as well, but this isn't a cancer biology class.
Re: (Score:2)
Cancer is a catch all for problematic cells that spread and harm the body. There may be an infinite number of ways a cell can start to go against its host. It may be impossible to
Re: (Score:2)
There are two ways for cell death - the first is the cell detects something is seriously wrong and commits suicide. The other way is the immune system sees there's something wrong with the cell and orders the cell to kill itself.
Both happen all the time and naturally. If you wonder how the immune system can detect it, it's basically because the cell shows the immune cells a sample of the proteins it makes and they're put up for inspection.
Either way, it looks promising.
The problem with cancer is that it's n
Re: (Score:2)
Like how the cell detects mutations and orders its own suicide, or how cancer disables it and fakes it well enough to evade it.
These aspects are actually very well understood. There has been a LOT of research done on this topic.
Suicide? (Score:4, Funny)
I did not RTFA, but I'm going to guess they post nasty things about the cells on social media until they lose all hope.
Re: (Score:3)
I did not RTFA, but I'm going to guess they post nasty things about the cells on social media until they lose all hope.
Scientists have developed a speaker small enough to play Coldplay at the cellular level. A few hours of that any anyone would want to end their suffering.
Re: (Score:2)
It's catfishing, at a cellular level.
A bit more computer power and it's done (Score:3)
Imagine being able to scan a cancer cell and shortly thereafter synthesize an injection that'll cause all its friends to commit suicide.
Maybe not until after I'm dead of old age, but also maybe in the next decade. It's going to be interesting. I have a friend going through chemo right now and it'd be nice to see that become a thing of the past.
CLICK HERE (Score:3, Funny)
Name it the James Kirk method (Score:5, Funny)
Re: (Score:1)
We have that now, it's called "CrowdStrike".
Historical note (Score:2)
This builds on the researcher's earlier work in the same vein which consisted of forcing the cancer cells to listen to the baby shark song repeatedly until they died. This was extremely successful, but poorly selective in that it was also toxic to non-cancer cells and the lab technicians conducting the experiments.
prostate (Score:2)
Maybe the same method can be used to reverse BPH, since the problem with an overgrown prostate is lack of apoptosis. And, PSA is a good marker to use.
tell them they are fat (Score:2)
Tell the cancer cells they are poor, fat, and stupid. They will either become NASCAR drivers or take their own lives. Its a win/win.