Coverage of Caltech’s “Cancer Fighting” Nanoparticles is Over-Hyped and Premature

11 14 Loading
nanoparticle in cancer cells

Caltech's research has shown that it can get nanoparticles and RNA into cancer cells. Cool, but this isn't a cure for cancer yet.

Maybe you’ve read about the amazing “cancer-killing nanobots” from Caltech that use RNA as a weapon. They’ve been making waves in news media all week.  The truth is that many headlines, and stories, are grossly misleading. Caltech, along with biotech firm Calando, has developed a method of using nanoparticles to cause RNA interference in cancer cells. The news has caused a nice jump in the stock of Calando’s parent company, Arrowhead Research (NASDAQ: ARWR). But all the talk about Caltech striking a major blow against cancer is premature. We don’t know if this RNA interference will actually destroy cancer cells, or even be safe to use  because it’s still in phase I clinical trials. As often happens with science linked to cancer research, the media has over-hyped a promising technology, pressuring it to perform before it is able.

What’s even more aggravating is the often hilarious misuse of the term ‘nanobots’. Look at some of these headlines:

or the even more unfortunate rehash:

‘Nanobots’ conjures up images of tiny little robots in the minds of readers, maybe even tiny little spaceships floating through the body. That’s just not what Calando created. Their nanoparticle is a 70nm spheroid with RNA embedded inside. When it’s absorbed into a cell, the particle falls apart, releasing the RNA. If we have to use a bad metaphor for it wouldn’t Trojan Horse be more apt? Maybe nano-grenade?

RONDEL

This is a nanoparticle, not a nanobot. Maybe we can compromise and call it a RNA-fueled nano-grenade?

The truth is that the first real ‘nanobots’ we use aren’t even going to look like robots. They’ll be our own cells that have been commandeered to perform other tasks, or they’ll be tiny spheres that float through the body and act very similar to cells or other biological systems.

Even forgetting the nanobot issue, I still think the Caltech research is  being over-hyped. The  nanoparticle has been found to reliably show up in cancerous cells and deliver strands of RNA that disturb the creation of a certain protein. According to the paper recently published in Nature, this is the first time that a nanoparticle has been shown to systematically appear in higher levels in a cancer cell as the dose to a patient increases. The Caltech/Calando nanoparticle system is called RONDEL, and according to Nature News, it targets cancer cells by the “leaky” blood vessels that often connect to them. While that targeting method now has proven dose-dependence (that is, more nanoparticles in blood equals more in cancer cells), there’s no reliable measure of its potency. Does it kill cancer cells? Does it even slow their growth? Is this RNA interference actually going to be an effective treatment?

For that matter, we don’t know anything about it’s safety either. Does it ever target the wrong cells? Doctors have biopsied skin melanomas (the cancer used in the trials) and found RONDEL in good amounts, but I can’t find any mention of how often it makes its way into non cancerous cells.

RONDEL delivers RNA, a special version (siRNA) that is double stranded and that interacts with a cell’s programming to “turn off” a certain protein. That’s a very cool system, and the original discovery of this RNA interference earned the 2006 Nobel Prize in Medicine (for work performed in 1998). The biopsies of cancer cells showed all the signs of RNA interference: cleaved RNA strands, lower protein levels (in one case), and disrupted messenger RNA. That’s great, but again, we have no idea if this RNA interference will translate into real-world benefits for a patient.

The problem is that we’re talking about only one aspect of a phase I clinical trial that isn’t even over yet. We won’t know the results (i.e. safety and efficacy) until later in the year. And the trial is only on 15 patients. That’s a tiny dataset.  It would take phase II and phase III (years of testing) before we’re sure this is really a proven way to “fight-cancer”. The discovery of nanoparticles in cancer cells is like knowing gasoline got to the engine in your car. It’s an important step, but it doesn’t give us any clue as to whether or not the car is actually driving down the road.

Caltech’s research and Calando’s nanoparticle are promising. A reliable means of creating RNA interference in a cell could be a great mechanism to fight cancer, to provide gene/protein therapy, and may have other powerful applications. It’s just too soon to know how reliable RONDEL is at the moment. Dose-dependence is just one factor we care about, we also need to know how selective that delivery is. And we have no idea about how effective this particular RNA interference trial will be in actually fighting cancer. It’s just too soon to say. For now, let’s praise this research for creating a RNA interference delivery system with proven dose-dependence and call it a day.

[Image credits: Caltech: Swaroop Mishra, Derek Bartlett]
[source: California Institute of Technology, Calando Pharmaceuticals, Nature]

Discussion — 14 Responses

  • Emanuel March 24, 2010 on 9:16 pm

    Thanks for the article, that was very informative. I haven’t been keeping up with the hype, but I’m glad someone took the time to write a clear, level-headed article about the research :)

  • Emanuel March 24, 2010 on 5:16 pm

    Thanks for the article, that was very informative. I haven’t been keeping up with the hype, but I’m glad someone took the time to write a clear, level-headed article about the research :)

  • Ross March 25, 2010 on 2:10 am

    What is happening with the LIFT(Leukocyte InFusion Therapy) cancer therapy? That seemed to be hugely promising, but like everything else promising in cancer treatment has disappeared off the radar.

  • Ross March 24, 2010 on 10:10 pm

    What is happening with the LIFT(Leukocyte InFusion Therapy) cancer therapy? That seemed to be hugely promising, but like everything else promising in cancer treatment has disappeared off the radar.

  • paul March 25, 2010 on 3:19 am

    Cancer cures that don’t work, work feebly or randomly, or are 20 years from market are announced every day–and that’s no exaggeration. I’ve read about cancer cures in the news all my adult life (and I’m getting old) but people are still dying of cancer.

    Wake me up when we have something that really works.

  • paul March 24, 2010 on 11:19 pm

    Cancer cures that don’t work, work feebly or randomly, or are 20 years from market are announced every day–and that’s no exaggeration. I’ve read about cancer cures in the news all my adult life (and I’m getting old) but people are still dying of cancer.

    Wake me up when we have something that really works.

  • Ed March 25, 2010 on 3:23 pm

    I don’t know where the over-hyping is coming from!!! The article talks about research being done and the “potential” benefit it may bring in the future. All research is important and needs to be carried out.
    Yes Paul…people are dying every day from this dreadful disease, but the life expectancy for those stricken with it are also increasing every day, and that is because of the ongoing research.

  • Ed March 25, 2010 on 11:23 am

    I don’t know where the over-hyping is coming from!!! The article talks about research being done and the “potential” benefit it may bring in the future. All research is important and needs to be carried out.
    Yes Paul…people are dying every day from this dreadful disease, but the life expectancy for those stricken with it are also increasing every day, and that is because of the ongoing research.

  • Daz March 29, 2010 on 5:40 am

    Hmmm, sorry but you don’t seem to understand what you are talking about. The significance of this paper is that is demonstrates for the first time that an intravenously injected nanoparticle can specifically target an interfering RNA to a tumor. Interfering RNA (RNAi) has been shown many time to be a safe way to hit cancer- the problem has been how to get the payload to the cancer in a ‘real world’ system (ie a mix of non-cancer and cancer cells as found in a real patient’s body. All sorts of delivery systems are being tried, but many are very indiscriminate, and they physially disrupt normal healthy cells . This physical disruption is the problem- the RNAi payload is not, because it is usually specific to a cancer only gene.

    I think this paper may be highly significant, because it is a generic carrier system for getting RNAi therapies effectively into diffuse tumours around the body. There are lots of RNAi cancer therapies proven at a cell culture or animal testing level, it is the lack of a delivery technology that has stalled their progress. This nanoparticle could be the generic system to piggy-back dozens of different RNAi drugs to their targets.

  • Daz March 29, 2010 on 1:40 am

    Hmmm, sorry but you don’t seem to understand what you are talking about. The significance of this paper is that is demonstrates for the first time that an intravenously injected nanoparticle can specifically target an interfering RNA to a tumor. Interfering RNA (RNAi) has been shown many time to be a safe way to hit cancer- the problem has been how to get the payload to the cancer in a ‘real world’ system (ie a mix of non-cancer and cancer cells as found in a real patient’s body. All sorts of delivery systems are being tried, but many are very indiscriminate, and they physially disrupt normal healthy cells . This physical disruption is the problem- the RNAi payload is not, because it is usually specific to a cancer only gene.

    I think this paper may be highly significant, because it is a generic carrier system for getting RNAi therapies effectively into diffuse tumours around the body. There are lots of RNAi cancer therapies proven at a cell culture or animal testing level, it is the lack of a delivery technology that has stalled their progress. This nanoparticle could be the generic system to piggy-back dozens of different RNAi drugs to their targets.

  • Emma March 31, 2010 on 9:13 am

    I definitely think that you guys need to first understand the way RNAi works. It’s not just any other drug – it’s a targeted therapy, the effectiveness of which lies in its method of having RNA base pairs specifically to the gene sequence(s) or regulatory gene sequences responsible for the cancer. In that way, you can’t really have a “wrong” target … because the point of this is that it base pairs SPECIFICALLY to the mutated gene involved.

    The hype originally began with RNAi itself, but the reason why this nanotechnology breakthrough has become extremely high on our radars is due to the fact that we finally have found a delivery method.

    Honestly, I understand why you guys are being skeptical about this simply because there have been tons of false alarms throughout this quest for cancer treatment. But, honestly, read more about it first before you judge.

  • Emma March 31, 2010 on 5:13 am

    I definitely think that you guys need to first understand the way RNAi works. It’s not just any other drug – it’s a targeted therapy, the effectiveness of which lies in its method of having RNA base pairs specifically to the gene sequence(s) or regulatory gene sequences responsible for the cancer. In that way, you can’t really have a “wrong” target … because the point of this is that it base pairs SPECIFICALLY to the mutated gene involved.

    The hype originally began with RNAi itself, but the reason why this nanotechnology breakthrough has become extremely high on our radars is due to the fact that we finally have found a delivery method.

    Honestly, I understand why you guys are being skeptical about this simply because there have been tons of false alarms throughout this quest for cancer treatment. But, honestly, read more about it first before you judge.

  • magrathea April 4, 2010 on 8:09 pm

    It’s not the first delivery method of RNA to cancer cells. Something similar is being tested by australian company (engeneic). They shoud publish results of their phase I clinical trials in a few months

  • magrathea April 4, 2010 on 4:09 pm

    It’s not the first delivery method of RNA to cancer cells. Something similar is being tested by australian company (engeneic). They shoud publish results of their phase I clinical trials in a few months