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RNA-Loaded Nanoparticles Fight Cancer
DirkDaring writes "It's been promised for years: that nanoparticles offer a treatment to many forms of cancer. Today, an important first step has been announced. In a new human trial, nanoparticles carrying RNA have successfully reached cancer cells and silenced the target gene. 'The researchers developed a nanoparticle carrying a molecular marker that binds to the surface of cancer cells, triggering the cells to absorb it. The siRNA carried within the particle was designed to silence a gene called ribonucleotide reductase M2 (RRM2), which regulates DNA synthesis and repair and is known to be an anticancer target. Because it was the first trial using targeted RNAi delivery for cancer, says Mark Davis, a professor of chemical engineering at Caltech and the study's lead author, "we wanted to choose a gene that was suspected to be hugely upregulated in a broad spectrum of cancers" in order to increase the likelihood of being able to observe the novel therapy's effect. The researchers analyzed biopsy samples from three melanoma patients in the trial who had received different doses of the therapy. They tracked the particles in the different samples, finding that the amounts they could see in the tumor cells correlated with the doses the patients received.'"
I wonder if this technique could be used for other diseases, e.g. arthritis?
Free Martian Whores!
Since the marker attaches to cancerous cells only, healthy ones should suffer no damage. Then again, I read the story above, so it's not like I'm specially insightful.
The most interesting part here is not about directing damage, it is that this was a successful non-topical application of siRNAs. In most tests up to now, siRNAs have been injected directly into the target tissue. This study shows a delivery system that carries the siRNA specifically into targeted cells via the bloodstream. In the long run, this might be the key to target metastases however small they are and wherever they are.
Ubi solitudinem faciunt, pacem appellant.
That's the beauty of this technique. With other therapies like chemo, surgery, or radiation, there is damage to non-cancerous tissue, and those don't kill 100% of the cancer, either. With this you could theoretically continue treatment, as with traditional treatments you can't.
There is still the problem of diagnosing the cancer early enough; this wouln't have helped Linda.
Free Martian Whores!
TV Personality: And how many people have you treated so far?
Dr. Alice Krippin: Well, we've had ten thousand and nine clinical trials in humans so far.
TV Personality: And how many are cancer-free?
Dr. Alice Krippin: Ten thousand and nine.
TV Personality: So you have actually cured cancer.
Dr. Alice Krippin: Yes, yes... yes, we have.
Cue destruction of humanity by albino gymnasts.
But if you, as a grandparent, can ensure the survival of your children and grandchildren, then mutations which elongate life make sense again, especially for species that rely on learned behaviour more than instincts.
As for cancer, I still assume that the cancer rate is coupled with the general mutation rate. If your species becomes too perfect in copying it's genes then it might be cancer-proof. But that also means that no changes occur in the germ line - you just became a static species! That mean you will probably die out because everyone else around you still evolves (the Red Queen's race). To summarize: Cancer and evolution have the same molecular basis! I wonder how this stabilized in living fossils....
Certainly it might be *possible* [...]
Yes, as a true scientist that is the correct answer, and here lies the problem: This non-denial gives this idea all the credibility it needs to run off as pseudo science. And once again the following holds:
The trouble with the world is that the stupid are cocksure and the intelligent are full of doubt. --Bertrand Russell
Well, yes and no. You are absolutely right in that this isn't a permanent effect, in the sense that the DNA of the cancer cells is not altered at all. RNA interference is like putting a defender in the game to intercept a pass; if the defender leaves the field, the receiver will be open again. Translation of the ribonucleotide reductase gene will only be blocked as long as the interfering RNA is there to block the messenger RNA. However, ribonucleotide reductase is incredibly important; it's the enzyme that tears a hydroxyl group off of ribonucleotides and makes them deoxyribonucleotides. A cell cannot make DNA without it. The notion is that cancer cells being treated with RNAi will die during the course of treatment, with no way to replace them. If you get all the cancer, there is no way for it to "bounce back," and if you miss some, then at least progression has been seriously slowed.
On the point of receptors, that raises an interesting point. The nanoparticles used in this experiment target transferrin receptor, a cell surface receptor for the iron-carrying protein transferrin. Transferrin is highly upregulated in cancer cells because iron is required by many enzymes important to cell division (including ribonucleotide reductase, incidentally). Because it is so vital, cancer cells probably cannot just stop making transferrin. Developing a mutant form of transferrin that the nanoparticles cannot adhere to is a possibility, but there'd be a very narrow window of success (success from the cancer's POV). After all, cancer develops a transferrin receptor because it needs to get iron from transferrin- the same transferrin floating in your bloodstream your healthy cells uses. So whatever stealth transferrin receptor cancer cells come up to hide from nanoparticles still has to be compatible with real transferrin, or the cancer cells will be unable to divide.
"FDA staff reviewers expressed concern about the number of patients who were left out of the study because they died."