Terrible pop sci title that makes the work sound a bigger deal than it is. I thought that evolution of cancer under drug treatment would be described. But a more accurate title would be, Computer simulations of proteins show molecular mechanism of particular resistance mutations to imatinib that were previously characterized to increase ligand dissociation kinetics.
That is, certain mutations in the protein that the drug imatinib inhibits enable cancer cells to be more resistant to the drug. A previous experimental study by the researchers found that these mutations increase the rate of drug unbinding from the protein. The study here describes computer simulations of the protein and explains why the mutations lead to increased dissociation kinetics. An advanced algorithm was used to sample ligand unbinding events in simulation.
> Additionally, if rapid drug release could cause drug resistance, and clinicians can show this is happening, they may be able to re-activate the drug effectiveness by asking the patient to take the drug more frequently.
One would have thought they would have tried this even without a fancy computer simulation.
Without knowing the mechanism of resistance, you wouldn’t risk giving the patient more of a drug. Many resistance mechanisms remove or block the binding pocket drugs bind to. In those cases, adding more frequent dosing wouldn’t be helpful.
You might have tried something like this first in a mouse model too. But using a simulation to discover the resistance mechanism can be a much faster way to get your answer (and justify the expense of a mouse study). This study is quite exciting to see.
I am in a lab that does similar research on resistance to cancer therapeutics but using different computational modeling methods. This is really interesting stuff, as kinetics as a method of resistance has been something that we know is important from a biological perspective but hasn't yet been incorporated much in resistance modeling.
Unfortunately it’s not in sci-hub yet but I imagine it will be soon. You can also look at the authors’ own web sites — often they post their papers there
How is this relevant? He is interviewing a guy who tried something totaly different and it worked miraculously for him.
Are we truly living in a society where an actual good REAL WORLD practical effect/outcome that actually works is totaly dismissed just because "he didn't do it the way the medical establishment told him to"?
Here's what I believe leads to a lot of confusion: For most of the 20th century, chemotherapy usually meant small molecules that interfere with cell division, resulting in cellular death. Even in other mechanisms, it wasn't targeting a weakness specific to cancer, thus had many side-effects.
What's so special about Imatinib is it targets a fusion protein that is only present in a specific type of cancer. The target is called the BCR-ABL fusion kinase, because it is literally formed by portions of two genes - BCR, and ABL, on two different chromosomes being fused together when these. This drug is only able to bind that fused version, and hence has no impact on healthy (aka non-cancerous) cells. This was one of the first precision/targeted therapies of its kind.
What's super confusing is people eventually started calling these precision therapeutics "chemotherapy" as well, so the previous common-use meaning and layperson associations with the word became mostly muddled.
So - to drive the point home, with these targeted therapies, you can have immense benefit with minimal side effects. Not so much with the older stuff, which is also still used in many other types of cancers.
> people eventually started calling these precision therapeutics "chemotherapy" as well
I think it is, despite the fact that the word seems to indicate broader use. The original medication was called cytostatics, which stops cell growth or division. Wikipedia says it like this:
The term chemotherapy has come to connote non-specific usage of intracellular poisons to inhibit mitosis (cell division) or induce DNA damage...] The connotation of the word chemotherapy excludes more selective agents... The development of therapies with specific molecular or genetic targets, which inhibit growth-promoting signals ..., are now called hormonal therapies. By contrast, other inhibitions of growth-signals like those associated with receptor tyrosine kinases are referred to as targeted therapy.
That is, certain mutations in the protein that the drug imatinib inhibits enable cancer cells to be more resistant to the drug. A previous experimental study by the researchers found that these mutations increase the rate of drug unbinding from the protein. The study here describes computer simulations of the protein and explains why the mutations lead to increased dissociation kinetics. An advanced algorithm was used to sample ligand unbinding events in simulation.