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Medicine Technology

First Anti-Cancer Nanoparticle Trial On Humans a Success 260

An anonymous reader writes "Nanoparticles have been able to disable cancerous cells in living human bodies for the first time. The results are perfect so far, killing tumors with no side effects whatsoever. Mark Davis, project leader at CalTech, says that 'it sneaks in, evades the immune system, delivers the siRNA, and the disassembled components exit out.' Truly amazing."
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First Anti-Cancer Nanoparticle Trial On Humans a Success

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  • by RyuuzakiTetsuya ( 195424 ) <taiki.cox@net> on Wednesday March 24, 2010 @08:29PM (#31605820)

    Well, what's meaningful is that they all didn't up and die, and that a bigger round of testing is to go forward.

  • by Truth is life ( 1184975 ) on Wednesday March 24, 2010 @08:30PM (#31605828)

    The point of the study is to make sure that people don't explode when the procedure is performed, or for something similarly unpleasant to happen--it's a Phase I study, not a real effectiveness trial.

  • Not just cancer! (Score:5, Informative)

    by Nihiltres ( 1161891 ) on Wednesday March 24, 2010 @08:30PM (#31605834)

    From comments on TFA, "The Lab" writes: "a science editor would be more capable of pointing out what is really exciting here, which is the ability to stop cells from producing a given protein."

    I think the cancer aspect is great (if it works) but this has potential for curing a whole host of diseases.

    Now we just need to figure out how to change people's DNA on the fly.

  • by Anonymous Coward on Wednesday March 24, 2010 @08:37PM (#31605896)

    As long as the subjects have the same distribution as the population, this sample can be considered representative of the population. This means that they didn't pick 15 terminal patients and didn't pick 15 100%-survival-rate patients. You can achieve quite a lot when your sample is well selected.

  • Re:Targetting (Score:5, Informative)

    by reverseengineer ( 580922 ) on Wednesday March 24, 2010 @08:39PM (#31605922)
    The nanoparticles have a component that attaches to the transferrin receptor on the surface of a cancer cell. Transferrin receptors are highly abundant on cancer cells because iron (what transferrin carries) is needed for cell division processes. Coincidentally, this is a fact I learned the first time this story was posted a few days ago.
  • Re:Nice if true (Score:5, Informative)

    by spud603 ( 832173 ) on Wednesday March 24, 2010 @08:40PM (#31605942)
    How about Nature [nature.com]?
  • Re:SWEET SUCCESS (Score:3, Informative)

    by NigelTheFrog ( 1292406 ) on Wednesday March 24, 2010 @08:45PM (#31605980)
    Too bad this won't do anything for emphysema.
  • Re:Targetting (Score:5, Informative)

    by Kral_Blbec ( 1201285 ) on Wednesday March 24, 2010 @08:46PM (#31605986)
    Incorrect. There are significant physiological and genetic differences between cancerous cells and normal cells. It would be entirely possible to target the RNA sequence to only bind to malignant cells and ignore normal ones.
  • Re:Artificial virus (Score:2, Informative)

    by MobileTatsu-NJG ( 946591 ) on Wednesday March 24, 2010 @08:47PM (#31605996)

    So, they made an artificial virus...


  • Re:Targetting (Score:4, Informative)

    by Edmund Blackadder ( 559735 ) on Wednesday March 24, 2010 @08:55PM (#31606064)

    I see your point that this does not seem like the ordinary concept of targeting. But in pharmacology that is exactly what targeting is.

  • by brianleb321 ( 1331523 ) on Wednesday March 24, 2010 @09:11PM (#31606192)

    I cannot see anything meaningful coming from such a small sample size. It has potential but obviously much more research is needed.

    You can't just jump from rats to tens of thousands of humans. That's why the sample size is 15. That's why it's a Phase I trial. There are four phases of clinical pharmaceutical testing that follow preclinical (animals, in vitro, etc.) testing. Phase I normally tests a treatment in healthy humans in order to see the negative effects of the treatment (this is not necessarily the case in cancer treatments because all cancer treatments have significant negative effects). Phase I trials are only a couple dozen people, max. Successful Phase I trials allow for Phase II trials. These usually have one or two hundred people with the disease the therapy is intended to treat. In Phase II, they are mainly gathering pharmacokinetic data (half life, metabolism, volume of distribution, etc.). Phase III is where you start to see the trials you're clamoring for. These are typically done in several thousand patients, all with the disease in question. These trials are placebo-controlled, randomized, double-blind studies (the hallmark of research). Statistical analysis then allows you to determine if the therapy was effective in improving outcomes. If so, the drug goes to the FDA. 30 days later, it is officially on the market. Phase IV studies begin here, and continue perpetually. They are called post-marketing surveillance, and they study long-term effects (because previous trials are not long enough to do this), as well as very rare adverse effects (where the sample size in previous trials may have been too small to correctly detect the progressive multifocal leukoencephalopathy that occurs in 0.1% of patients treated).

    So don't claim the study size wasn't big enough - it wasn't supposed to be. Phase III trials are what you want. Phase I and II trials are of no interest to anyone outside of health professions, really.

  • Re:Targetting (Score:5, Informative)

    by cortesoft ( 1150075 ) on Wednesday March 24, 2010 @09:20PM (#31606240)

    How else would you define targeting in this context other than to mean only binding to cancerous cells? It seems you are implying that targeting can only refer to conscious 'aiming', but that is only a subset of things that can be considered targeted.

    Targeted can mean 'select as an object of attention or attack'. That is what they are doing when the design a drug.. selecting cancer cells for attack, and then designing the drug so it will only effect those cells. Check out http://en.wikipedia.org/wiki/Drug_design [wikipedia.org]

    Targeted drugs DO mean something specific in pharmacology.

  • Re:Isn't this... (Score:2, Informative)

    by Trebawa ( 1461025 ) <trbawa@@@aol...com> on Wednesday March 24, 2010 @09:30PM (#31606330)
    You'd have to engineer particles that target a specific vital tissue (and stop thinking "brain", because the blood-brain barrier would block that), and then deliver a piece of siRNA that silences an essential gene for that tissue. You'd also have to inject enough of these into the person to have this effect. Still, it could be useful to replace the siRNA entirely with some kind of toxin (it would be nearly undetectable, because it wouldn't linger in the bloodstream).
  • The first? Hardly... (Score:3, Informative)

    by QuietLagoon ( 813062 ) on Wednesday March 24, 2010 @10:09PM (#31606558)
    Abraxis BioScience [abraxisbio.com] is a fully integrated biotechnology company dedicated to delivering progressive therapeutics and core technologies that offer patients and medical professionals safer and more effective treatments for cancer and other critical illnesses. The Abraxis portfolio includes the world's first and only protein-based nanoparticle chemotherapeutic compound (ABRAXANE) which is based on its proprietary tumor targeting system known as the nab(TM) Technology platform. From the discovery and research phase to development and commercialization, Abraxis BioScience is committed to rapidly enriching the company's pipeline and accelerating the delivery of breakthrough therapies that will transform the lives of the patients who need them.


    Abraxis has been around for, literally, years.

  • Re:Targetting (Score:3, Informative)

    by ShooterNeo ( 555040 ) on Wednesday March 24, 2010 @10:31PM (#31606678)
    Yes but the beauty of this treatment is that it's two stage. Once the RNA gets into a cell, it can be targeted to ONLY harm cells with the RNAs of cancer floating around in their cytoplasms.
  • by Oxford_Comma_Lover ( 1679530 ) on Wednesday March 24, 2010 @10:32PM (#31606694)

    > everything is known to cause cancer in California... I could never figure it out, so I just stay away from California.

    Everything says it causes cancer because of Proposition 65 [wikipedia.org]. Basically, if something in California is known to cause cancer (even only if ingested by the ton), you have to label it, or lawyers can sue you under a "private attorney general" law. In theory it might be a good idea, but it was implemented so that the defendant has the burden of showing that it's basically impossible to the nth degree that the thing could cause cancer in the quantities you're talking about.

    This resulted in a lot of litigation where basically lawyers went around everywhere and said "Oh! You have flame-retardant furniture! Did you know it can cause cancer if you lick it?" "You're a dentist! You use drugs that can cause cancer if you administer them for a week and you didn't post a notice!"

    This resulted in a plethora of notices to prevent lawsuits--notices which the public ignores because they're on everything. So in the cases where the warning is actually important, it gets ignored because there are so many.

    IIRC, there have been some efforts by the AG (and some courts) to limit abuse.

  • by Gumby ( 425 ) on Wednesday March 24, 2010 @11:35PM (#31607052)

    http://media.caltech.edu/press_releases/13334 [caltech.edu]

    If you cannot spell Caltech properly - please turn in your nerd card.

  • Re:Targetting (Score:5, Informative)

    by amRadioHed ( 463061 ) on Wednesday March 24, 2010 @11:43PM (#31607110)

    Well, the summary says that the results have been perfect so far, so that's a real good sign. Frankly something like this sounds too good to be true, but every once and a while breakthroughs do happen, so we can hope!

  • by BitZtream ( 692029 ) on Thursday March 25, 2010 @12:22AM (#31607248)

    Self reply ...

    I just feel I should clarify, in order to get the perfect distribution you need a sample size at least big enough to all possible variations in the distribution in the ratios present in the population.

    I.E. The samples too small to provide useful statistical results. Its just a general indicator.

    If all 15 people live perfectly for a normal life after this it doesn't mean its 100% safe, it just means its highly likely to work well on a lot of people, but its entirely possible that those 15 people happened to share something that no one else has. Likewise if all 15 people die tomorrow, its a really good indication that this isn't going to be that useful on the population, but it doesn't mean that everyone will die from it ... those 15 people may just have been exposed to a secondary compound since they are all early test subjects that happened to interact and kill them.

    The sample size is just too small to provide truely useful stats when it represents about 4 bits of diversity in a population that is defined by a code that allows for 38 bits of variation currently representing about 33.5 bits of that.

    Its funny how engineers like to over sample. An engineer wouldn't accept a sample size less than 39 bits to be safe, even though the total population is smaller than that currently. Statisticians on the other hand are happy with pretty much any number greater than 1 bit.

  • by Puff of Logic ( 895805 ) on Thursday March 25, 2010 @12:44AM (#31607312)
    Phase III trials in this situation would assess the efficacy of this treatment relative to the current standard of care. The whole point of phase III is to figure out whether the drug is at least as effective as the current standard and, as you correctly state, it would be medically unethical to administer a placebo treatment to a cancer patient.
  • Re:Targetting (Score:5, Informative)

    by wickerprints ( 1094741 ) on Thursday March 25, 2010 @01:04AM (#31607362)

    Why is this the first example of the concentration of nanoparticles showing a correlation with the initial dose? To me it seems obvious that this would happen, so I'm curious as to what normally prevents this.

    The dose-response characteristics of a substance carries important information about its pharmacokinetics, such as how rapidly it is metabolized and excreted. It is NOT obvious that increasing dose always results in increased concentration in the targeted tissue(s), just as it is the case in chemical reactions in which increasing the proportion of one reagent may not necessarily increase the yield. For example, increasing dosage may also increase hepatic clearance. What the researchers demonstrated basically boils down to this: the nanoparticles' activity is highly specific to the tumor cells and does not get "broken down" or excreted proportionally higher as the dose increases. Such characteristics are highly desirable.

  • Re:Targetting (Score:5, Informative)

    by interkin3tic ( 1469267 ) on Thursday March 25, 2010 @01:51AM (#31607524)

    It would be entirely possible to target the RNA sequence to only bind to malignant cells and ignore normal ones.

    Yeah but chemotherapy and radiotherapy work the same way. The problem is that the characteristic of cancerous cells they bind to is the fact that they grow fast.

    No they don't work the same way. Radiotherapy, and most current gen chemotheraputics, work against all dividing cells. It sounds like these nanoparticles use a specific protein (NOT rna) to bind to the cancer cell, then once inside they cause RNAi (this is where the RNA comes in) to knock down a specific gene transcript.

    I obviously don't know the specifics, but if you make a nanoparticle that binds to and is taken up by cells expressing a specific growth factor, that's -not- going to be taken up by all cells. There are a lot of growth factors, and often in cancers, growth factor receptors are expressed far more than they normally are. So the targets are found only on some cell types, and there are hundreds more on the cancer cells than the healthy cells.

    Furthermore, you could target individual genes to be knocked down by the RNAi effect, potentially genes that aren't even expressed by the normal cells which are expressing the receptor you're targeting. I'd guess for maximal efficiency, you'd be targeting housekeeping genes that all cells needed, but in principle you could make it a gene that cancer specifically needed.

    Both levels of specificity, even if they're not used, are a far cry from "damage every dividing cell and hope you kill the cancer before you kill the dividing tissues the patient needs to survive." And they don't actually use RNA to bind to the cell, they use protein to target the cell and RNA once inside the cell to target the specific gene. ... by the way, I am not a molecular cancer biologist.

  • by Gumby ( 425 ) on Thursday March 25, 2010 @02:20AM (#31607650)

    And that time they spelled Caltech correctly!

  • Re:Targetting (Score:3, Informative)

    by reverseengineer ( 580922 ) on Thursday March 25, 2010 @04:12AM (#31607954)
    Yes, normal cells could be expected to have a smaller density of transferrin receptors than cancer cells, but almost all cells could be expected to have some, given the importance of iron ions in cells. The reason transferrin receptors are of such interest is primarily a mechanical issue. Each of your cells is covered with complicated receptors that serve many purposes, and if you're looking for a way for cancer cells to stand out, there are many receptors involved in growth and division whose numbers are typically swollen on cancer cells. The issue is that most of the candidates simply meet messengers at the cell membrane, and pass along the information of the message into the cell via a second messenger. Others like the glucose transporters let cargo through a narrow and specific channel. When transferrin receptors bind to transferrin at the cell surface, however, a vesicle forms around the bound transferrin+receptor complex and pulls the whole thing inside the cell. Once deep inside, the transferrin is induced to let go of its iron ion cargo, and the iron-less complex heads back to the surface. Given that cells will essentially swallow anything that can be made to bind to a transferrin receptor, this could become an important future route for drug delivery.

    However, yes, it is like chemotherapy in that it will affect proliferating healthy cells as well as cancer cells (could be a lot less toxic in terms of metabolic clearance compared to current oncolytics). The protein they cut production on using RNA interference, ribonucleotide reductase, is already targeted by a few chemo drugs in use like gemcitabine. Any cell that needs to make DNA bases needs a working copy of ribonucleotide reductase; rapidly dividing cancer cells just have a much more urgent need. However, this nanoparticle/siRNA system has the advantage of being highly adaptable. Find a new oncogene target? Write a new siRNA to silence it, and you have the equivalent of a whole new class of cancer drug.
  • Re:Artificial virus (Score:4, Informative)

    by Elbows ( 208758 ) on Thursday March 25, 2010 @09:16AM (#31609484)

    I didn't see any indication that the nano-particles are self-replicating, or capable of spreading from one person to another, so you'd need to inject each target individually. It's probably easier just to shoot them.

    Plus, if I understand correctly, cultural conceptions of race don't map very well to genetic differences. So finding a race-specific gene to target might be harder than you'd think.

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