Nanotechnology and cancer treatment: Do we need a reality check?

by Andrew Maynard on March 2, 2010

Cancer treatment has been a poster-child for nanotechnology for almost as long as I’ve been involved with the field.  As far back as in 1999, a brochure on nanotechnology published by the US government described future “synthetic anti-body-like nanoscale drugs or devices that might seek out and destroy malignant cells wherever they might be in the body.”  Over the intervening decade, nanotechnology has become a cornerstone of the National Cancer Institute’s fight against cancer, and has featured prominently in the US government’s support for nanotechnology research and development.  And for good reason – nanotechnology holds the promise of treatments that can diagnose cancer earlier in the disease’s development than ever before; treat tumors using lower concentrations of chemotherapy agents, and target malignant cells while leaving healthy cells untouched.  Like many of my colleagues, I have used emerging nanotechnology-based cancer treatments as a compelling example of what is possible when we gain mastery over materials at the scale of the atoms and molecules they are made of.

So I was somewhat surprised to see the eminent chemist and nano-scientist George Whitesides questioning how much progress we’ve made in developing nanotechnology-based cancer treatments, in an article published in the Columbia Chronicle.

According to the article,

George Whitesides, professor of chemistry and chemical biology at Harvard University, said that while the technology sounds impressive, he thinks the focus should be on using nanoparticles in imaging and diagnosing, not treatment.

The problem lies in being able to deliver the treatment to the right cells, and Whitesides said this has proven difficult. “Cancer cells are abnormal cells, but they’re still us,” he said.

Whitesides went on to comment that

“It’s easy to say that one is going to have a particle that’s going to recognize the tumor once it gets there and will do something that triggers the death of the cell, it’s just that we don’t know how to do either one of these parts”

This got me thinking – because George is a smart guy and well worth paying attention to – have we somehow got so caught up in the possibilities of nanotechnology in treating cancer, that we have lost sight of the realities?

To get a better sense of where we are on nanotech-enabled approaches to treating cancer, I asked a handful of experts working in the field the following question: “What are some of the more significant science challenges researchers face in developing nanotechnology-based cancer treatments?” The responses were cautious, and clearly cognizant of the hurdles to taking scientific and technological breakthroughs out of the lab and into the market.  Yet despite this, there was an over-riding sense of optimism running through them.

Steve Rosen, Director of the Robert H. Lurie Comprehensive Cancer Center at Northwestern University commented:

“I feel nanotechnology has the possibility of revolutionizing both in vitro and in vivo cancer diagnostics.  Therapy always remains a greater challenge and in the short term I see nanotechnology as a vehicle to enhanced delivery. The long term prospects are substantial and limited only by the creativity of individuals involve in this area of investigation.”

This was echoed by Tyler Jacks, Director, David H. Koch Institute for Integrative Cancer Research at MIT:

“Nanotechnology holds great promise for cancer therapy, in my view. That said, there is need for more research to learn the best strategies to specifically direct the nanomaterials to cancer cells following systemic administration. This will require overcoming the body’s natural filtration systems as well as optimizing the methods for tumor-specific targeting. It may be that truly tumor-specific targeting will require combinatorial approaches.”

The difficulties of overcoming biological barriers to using nanoparticles effectively in treating cancers were expanded on by Martin Philbert, Senior Associate Dean at School of Public Health, University of Michigan:

“The body’s immune system is primed to recognize particles of the size range encompassed by most therapeutic and imaging nanotechnologies.  Since elements of the immune system are coordinated and disseminated throughout the body, a major challenge is the design and fabrication of nanotechnologies that will either avoid immune cells or use them to achieve appropriate targeting without activation or suppression of immune function.

A second major hurdle is elimination from the body.  Many of the newer nanoparticles are designed to be eliminated from the body by either being ‘small’, i.e., less than 8 nm in diameter to facilitate passage with the urine out of the kidneys, or to dissolve to a size that allows for elimination through the urinary flow.  Nevertheless, the kinetics of elimination are invariably altered by the ability of the reticuloendothelial portion of the immune system to take up these materials and sequester them in lymphatic organs or interstitial spaces for longer periods than anticipated.”

Yet despite thee challenges, progress is clearly being made.  Piotr Grodzinsky, Director, Nanotechnology Cancer Programs at the National Cancer Institute noted that

“Nanotechnologies for medical applications have been maturing. Several therapeutic formulations entered clinical trials and are expected to have an impact on how cancer treatment is done in the future. Similarly, multiplex diagnostic platforms with high sensitivity and specificity are proving themselves in testing of clinical specimens and will contribute to early disease detection.”

Scott McNeil, Director of the Nanotechnology Characterization Laboratory cautioned that

“Developers of nanotech-based therapeutics face preclinical challenges that may be more involved than development of small molecule drugs…”

but went on to add

“…the payoffs are now being demonstrated in clinical trials by several companies. We are observing a consistent trend towards decreased toxicity for nanodrugs compared to their small molecule counterparts.”

And in responding specifically to Whitesides’ comments, Jim Baker, Director of the Michigan Nanotechnology Institute for Medicine and the Biological Sciences, observed that

“[George Whitesides] is correct that this is a very complex problem, with cancer as a variation of self being a central issue.  In addition, the concept of some in the material science community that nanoscale materials would be inherently better ignores potential problems related to biocompatibility and the necessity of this material to function in a wet environment.  Additionally, the concept of a “nanomachine” is fundamentally flawed because having mechanical devices of this size violates the laws of physics.  What is moving forward are bio-inspired materials that will provide incremental improvements in drug delivery and imaging that could not be accomplished with traditional materials.  Each one will be unique, however, and require its own evaluation for efficacy and toxicity, just like any other drug.  This provides a difficult hurdle, given the costs and clinical evaluations that are involved.”

Reading through these comments, I get the sense that we’re only beginning to scratch the surface of what working at the nanoscale can do for cancer treatment.  Certainly there are hurdles to be overcome – some of them significant.  And it’s important to remember that the road between lab-based discoveries and real-world treatments is a long and arduous one – even the most promising therapies can take years or even decades to get to the point where they are widely available.  Yet it’s hard to avoid being caught up in the enthusiasm of scientists working on nanotechnology-enabled cancer treatments, or not to  be inspired by what might be achieved through engineering increasingly sophisticated therapeutics at the nanoscale.

That said, expectations on how nanotechnology will impact cancer treatment clearly need to be tempered.  In this respect, I thought that the comments from Jennifer West, the Isabel C. Cameron Professor of Bioengineering at Rice University, were particularly well-grounded:

“Nanotechnology isn’t a magic solution to cancer, but provides additional tools in the arsenal, some with new and unique properties.  As with any cancer therapy, the key issue is to get the therapeutic agent to tumor sites and metastases at high concentrations, then destroy cancerous cells while minimizing damage to normal cells.”

Nanotechnology is clearly not a panacea.  It provides exciting new opportunities for treating cancer.  But its use also faces many scientific, economic and regulatory hurdles.  Yet the idea of crafting more effective cancer treatments by engineering matter at the nanoscale remains a compelling one – if only we can work out how to translate the idea into practical solutions.

As one of my sources – who preferred not to be named – commented:

“I don’t think that the field needs a reality check but rather ways to move more of the discoveries and developments into humans”

1 Kyle Kmenex March 2, 2010 at 4:01 pm

Thoroughly thought provoking article. Your anonymous contact’s quote i believe is most important for innovators, considering that it speaks directly to the logistics of science.
Indeed… If science wants a revolution it shall be within the logistics of collaboration and information sharing. Our expertise in sensing and modeling are increasing regardless of the state within consumer application, and rather then become bogged down in finding applications too soon we should instead invest in a solid foundation from which to manage all of this information.

2 Kevin Eddy March 2, 2010 at 4:13 pm

Speaking strictly as a non-technical (at least on nanotechnology) observer with a close relative dying from cancer right now and a mother who succumbed to it 35 years ago…

I did not agree with Whitesides when I first read his quote, but it should be obvious to anyone on reflection that destroying cancer cells or stopping the spread of cancer is only one part of the battle. We can do that right now with a wide variety of methods. A single explosive device can kill all the cancer cells in several individuals in a heartbeat.

The trick of course is to kill the cancer without killing the patient.

Cancer treatment today uses plenty of generally destructive methods – surgical removal of affected and surrounding tissues, radiation, and chemo, etc. I’m not a doctor but I can see the treatments slowly killing my brother’s wife as they try to kill the cancer or even just slow it down.

My hope is that researchers will soon find ways to better identify and target the diseased cells, and destroy them without destroying the healthy ones. I don’t care if it is a nanobot or nanodrug or laser or that little cylinder shaped thing Doctor McCoy used in Star Trek. I want my sister in law to live and be free of cancer.

3 Andrew Maynard March 2, 2010 at 5:09 pm

Thanks Kevin. I think this is the “reality check” that’s needed – cancer is nasty; current methods of treating it – while effective in some cases – are relatively crude; and we need to pursue every avenue that opens up to develop better treatments. Even where there seems to be a disconnect between what nanotechnology promises and what it currently delivers, we would be remiss not to follow up on this promise – along with every other lead towards diagnosing and treating cancer more effectively.

4 David Colquhoun March 2, 2010 at 6:01 pm

Yes of course the possibilities should be investigated. And wheb there are some results they should be published. The constant over-hyping is doing real harm to science. It isn’t restricted to nanotech of course. I guess it is part of the internal war to win funds, and to boost the vanity of the investigator. But from the outside it looks like a form of dishonesty. It has gone a lot too far already.

5 Hilary Sutcliffe March 3, 2010 at 4:18 am

Helpful Andrew thanks, I was wondering. Though speaking to some of the front line companies they are more optimistic too, not sure if this is natural business optimism and hype or reality. I have asked them to put a comment on your site!

6 Andrew Maynard March 3, 2010 at 9:20 am

Thanks Hilary – looking forward to any comments that arrive! I should note btw that a number of the people I had comments from above are also involved with developing commercial products.

7 Ivan Amato March 3, 2010 at 8:10 am

Nanotechnology is a logical extension of the microscale technology that has infiltrating the world for decades and it is inherent as a conceptual framework in the miniaturization vision that Richard Feynman articulated in his famous 1959 talk, There’s Plenty of Room of the Bottom. In the 1980s, as investigators began developing more tools (like scanning probe microscopes) for engaging the world on the nanoscale, the discourse about nanotechnology revved up, and it took root with the language of futurists, most notably that of Eric Drexler and his ilk, who were comfortable with thinking in terms of 5- year timelines. Even as the scientific and engineering communities have made great progress toward some of the visions of nanotechnology, that futurist discourse, I think, continues to set much of the tone. It certainly continues to feed the tension between visions of what could be and what is and what is practical, with nanomedicine being an example. It would be interesting to analyze the discourse surrounding chemical and materials technologies in the 1930s and 1940s and around medical technologies in the early years of antibiotics so see if similar tensions were part of all the talk back then.

8 Andrew Maynard March 3, 2010 at 9:18 am

Interesting idea Ivan, although my sense is that the dynamics of technology promotion are very different today – underpinned by the combination of a highly connected global population and the belief that marketing is critical to success.

9 Luisa Filipponi March 3, 2010 at 11:54 am

Thanks Andrew for this blog. You are raising a very good point. Actually in my efforts to communicate nanotech to young people I have been very cautious with using the “cancer treatment” as an example of nanotech application. Cancer is unfortunately a disease that affects directly or indirectly a lot of people, kids can have a parent or relative/friend with this disease. We (communicators) must be very careful in writing sentences like “…one day these nanoparticles could kill cancer”, they could create expectations and hope for a cure way too early. I read these kind of sentences very often. I had this kind of issue also when writing about the future treatments of spinal cord injury. If on the one hand we must make people aware of the tremendous potentials of nanotech in medicine, it is crucial to be balanced and honest. I think there is nothing worse than disappoint a person who is suffering.

10 Diana April 28, 2010 at 2:47 pm

Kudos Andrew for shedding light on an area, which clearly needs more attention!    

As a daughter who’s mother is going through stage 4 colon cancer, which was misdiagnosed for over 6 months, I find it irreprensible that we as a world, as a country, as a people, are not putting more money into research on technologies that hold more promise, such as nanotechnology, and instead continue to dump endless monies into old band-aid fixes, which we know will not work in the end.  

If we have a technology, which helps with diagnoses, why are we not integrating it into practice yet?  Everything you read on cancer mentions early detection is the key to survival. 

Instead “Chemo will kill you if the cancer doesn’t” — has become an all too common mantra that we’ve grown to accept . . . Why is that?    
     
Baker seemed to be the only one who brought up this issue of cost.  We need not look far to see how close our government, insurance companies, and pharmaceuticals are– and where the money gets spent.  

Unfortunately, it does come down to money– case in point, why would we be pushing back colonoscopies from once every 5 years to once every 10?  The sad truth– cancer has become a business.  

If only there were some true political pioneers who were willing to make a change and make LIFE a business instead, but then how would they get elected?  Who would help finance their campaigns?            

I came across an article on the web from 2004 ( http://nano.cancer.gov/objects/pdfs/Cancer_brochure_091609-508.pdf).  As a non-scientist, reading this article it seems the technology has been there, but we don’t appear much further along… And I have to ask why?  

Ironically, it mentions 2015 as a discovery date, which seems to pay credence to Filipponi’s argument of settting clear expectations.  Although, shouldn’t there be some sort of expectations or goals?  Withouth them we are hopeless.  People are dying, not just a few, and as previously mentioned that is the reality

11 Diana August 29, 2010 at 6:28 am

Just kind of surprised there was no response at all to my post???

12 Andrew Maynard August 30, 2010 at 3:41 pm

Hi Diana, and huge apologies for not responding earlier to your comment. I suspect others didn’t respond because it came after the initial flurry of interest in this piece – I don’t have the luxury of this excuse though!

First, I very much appreciate your comments, especially give how close to home this issue is for you.

Sadly, you are correct – cancer and its treatment is a business! Yet there are plenty of people in this business who do what they do because they want to make the world a better place. That’s the good news. The not-so-good news is that we still desperately need better ways of translating promising research into effective treatments – ones that primarily benefit patients rather than shareholders. And part of this must be focusing on prevention and early detection. The profits may be less, but the benefits will be substantially greater!

It still seems that, while we have an awful long way to go to develop a complete understanding of cancer and its treatment, there are exciting new technologies in the wings that will help detect and address certain cancers. Lets hope that we also learn to do better in how we enable these to develop into effective, available and affordable treatments.

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