Bill Doyle: Treating cancer with electric fields

rhody

TED Video: Treating cancer with electric fields
I found it amazing that patients wearing the radio therapy patches were able to carry on with their daily lives and without the dangerous debilitating side effects associated with chemo and radiation. Pretty interesting watching cell division being interrupted ending with the cells destruction due to the cells integrity being compromised by the applied frequencies.

Rhody...

Ygggdrasil

At first, I was very skeptical and thought that this idea looks like complete non-sense, but after looking into it, it seems somewhat legit. Doyle's company, Novocure, has made a device based on this principle that has undergone clinical testing (http://clinicaltrials.gov/ct2/show/NCT00916409) and has been FDA approved for treating brain cancer (http://www.webmd.com/cancer/brain-ca...umor-treatment). Various studies of the principle (for example, http://dx.doi.org/10.1073/pnas.0702916104) have been published in peer-reviewed journals.

Despite all of this, I still don't see why this device works. Supposedly, it works by disrupting microtubules during cell division (http://online.wsj.com/article/SB1000...538647642.html has a quick summary). First, I don't fully understand how and why microtubules are specifically targeted by the treatment. Second, even if the electrical fields do selectively disrupt microtubules, I still don't see why the treatment works because microtubules have other important roles in non-dividing cells, especially in the brain. For example, microtubules help to transport materials in the cell, a task that is especially important in neurons which have very long, extended processes such as its axons and dendrites. Because of this, it seems like the brain would be the area where you would want to avoid most with a treatment that acts by disrupting microtubles. Yet somehow, the device seems safe and seems to work?

Pythagorean

But do those cells divide?

bobze

You can catch the full FDA application and approval here.

Its not intended as a first use device and only intended to be used after chemotheraputic and surgical avenues are exhausted. Considering that GBM (glioblastoma multiforme) has such a terrible 5 year survival rate--I'm not convinced the very small increases in life span are real. I don't have time to look through their studies at the moment though, but my bulls%&$ meter is spiking--FDA device approval is, quite frankly, poorly regulated--And everyone in clinical medicine knows it. There is almost no oversight on device efficacy as compared to pharmacological agents. We did an interesting dissection of the terrible approval for stint-placement in certain stroke types. Though the FDA had approved the actually stints (pre-big head to head trial mind you), when research actually got around to a head to head, they found there was a significant increase in mortality with stint placement.


Turns out, most "medical devices" get to circumvent going in a head to head trial with standard of care (SOC) procedures and protocols. Why? That's a damn good question. It probably has a lot to do with political lobby unfortunately--Medical device manufactures just aren't held to the same standards as pharmaceutical companies.

No, regardless microtubule function is still very important in non-dividing neurons.

Pythagorean

But the article gives me the impression that it only affects microtubules under division conditions. Is this wrong?

Ygggdrasil

@Pythagorean: My understanding is that the researchers claim that the device will disrupt the microtubules that form the mitotic spindle, preventing cancer cells from dividing. This is an established means of targeting cancer and drugs like taxol work in this way. If the therapy targets only the mitotic spindle, it would indeed not affect non-dividing cells. But what I do not understand is how the field could specifically target only the microtubules involved in forming the mitotic spindle. It sounds like the treatment would disrupt all microtubules and therefore affect non-dividing cells as well.

@bobze: Thanks for the info about FDA device approval. I was wondering how something like this could get approved.

atyy

I don't wish to defend the device, just to discuss this heuristic. Could it be that disruption of cell division is more sensitive, say it never recovers if you disrupt it during a crucial 5 minutes, whereas axonal transport is so slow that if you disrupt it for say half an hour, there's enough time for it to recover without damaging the cell?

Penrose must be keeping a close watch on a wonderful way of testing his theory

bobze

Or it could simply be that the patients die too quickly to see significant side effects of non-dividing microtubule disruption.

Lets be honest, these are patients that are refractory to chemo treatments, are not good candidates for surgery and have an extremely, extremely aggressive cancer.

GBM is a grade 4+ glioblastoma. The median 5 year survival is 4%, even in patients who undergo surgical resection. Grade 5 and beyond has a 0% survival rate at 5 years out. The average survival rate from time of grade 4 diagnosis is something on the order of 11 months.

It generally presents in two ways clinically. In older people as lower grades which progress over 5 years to a grade 4 or in younger people as a grade 4.

IIRC (sorry I just glanced over the FDA paperwork) their target was prolongation of life at 1 year out. Possibly then, the patients simply die before any neurological sequelae arise.

Confounding the problem, this wasn't blinded. You can't blind a patient or their doctor when the patient is wearing an electrical device around their head. Ergo, was the very slight increase in life span a product of placebo? I don't know, I suspect it may be.

The medical community can't do a head to head with GBM chemos and placebo because of ethical conflicts, so all the placebo data was extrapolated from prior studies based on old and inefficacious chemotheraputics--Not current ones. Basically their bottom line on placebo control was "a guess".

Edit: To be honest, I don't know what kind of arguments you can make for quality of life either. We're talking of adding a month, maybe two to current standard of care (at least according to their research) for GBM patients at the a&*-end of a terminal illness. Can't say that would be a fun month or two. I've seen people dying of GBM, the last couple of months aren't pretty.

Edit2: I'm not saying that it isn't worth more research, or that they aren't possibly on to something. But, I think at this point we should remain rather skeptical of claims. And hailing this as "the next big thing" in cancer (brain) treatment is about as premature as a 18 year old on a hot date.

atyy

But what is the case for side-effects, or specifically neurological sequelae?

bobze

You mean the mechanism? It would be the devices intent of treatment: MT disruption.

Or do you mean what kind of side-effects could arise from MT disruption in mature neurons?
MTs are used to traffic all kinds of vesicular traffic around the neuron, such as getting non-synaptically produced neurotransmitters in place, etc. GoogleBing "neuronal trafficking and microtubules"--Then apply imagination liberally to disruption of those processes.

Pythagorean

It looks like they exploit the special geometry of cell division with the electric field alignment:

Experimental Therapeutics, Molecular Targets, and Chemical Biology:
Disruption of Cancer Cell Replication by Alternating Electric Fields
Eilon D. Kirson, Zoya Gurvich, Rosa Schneiderman, Erez Dekel, Aviran Itzhaki, Yoram Wasserman, Rachel Schatzberger, and Yoram Palti
Cancer Res May 1, 2004 64:3288-3295; doi:10.1158/0008-5472.CAN-04-0083

http://cancerres.aacrjournals.org/co...4/9/3288.short

rhody

I respect all of you ygggdrasil, pythagorean, atty and bobze, having said that I was hoping that somehow, someday, someone would make the video like the one I found claiming the "discovery" of "Tumor Treating Fields" by the Israeli Dr Palty. There is precedent and a large body of verifiable evidence that destroying cancer cells was performed in a similar manner successfully in the 1930's by Royal Rife, made possible by his remarkable microscope, an invention that for the first time used polarized light passed through crystals that suppress all rays except for those in one possible plane see except from news article and link to others here:



Without this invention, his breakthroughs at the time early this century would not have been possible. No model or blueprints exist of his original invention exist today, just pictures and descriptions, news clippings, etc. I spent quite a few months long before finding PF digging as I like to do over interesting people like this. You are all highly educated, skeptical, and I respect that. Having said that, I encourage you to start with this link and verify that Rife did in fact create this awesome microscope, then came up with a way to treat certain bacteria and cancer cells with radio waves directly observing their destruction with it and highly inventive methods of capturing target cell destruction.

I found it frustrating that many today are in the "Rife" business to try to sell a bill of goods based on his creative genius. Having said that, if you look at just the facts (in the main link provided), you cannot ignore some of his amazing contributions. Check out this newspaper science clipping from the link provided above (double click it to blow it up), it provides more detail than the picture I provided. I don't expect you to believe me. Prove it to yourselves.

You all know by now I am not a crank and do not easily believe things without proof. All that I ask is that you keep an open mind when reviewing, the deeper you go, the longer you take as the picture of Rife's early success and tragic end play out you may change your minds. In the end for me, it is not easy to dismiss Rife's work, although today largely destroyed and corrupted by those who seek to make money from his work, and those in the medical establishment who at first embraced then later discredited him. The evidence is there, judge for yourselves.

Let me finish by saying I am glad that Dr Palty's "discovery" is being given a serious look, FDA politics aside.

Rhody...

P.S. There are some broken links from the main link I posted here and there, but the body of them appear intact.

bobze

Rhody,

I like the enthusiasm, but there is something I want to point out that most lay-people to the field often don't get--Which is what makes the almost daily barrage of "miraculous cure for cancer just around the corner" claims possible.

Killing cancer cells in vitro (I'm a link) is small fish. "KILLS CANCER"!!!--so what? I can kill cancer cells all day long. To put it bluntly, killing cancer cells in vitro ultimately doesn't mean s***! I can take you into the lab, we can grow out lots of HeLa cells (cancerous cells) and I can literally show you hundreds of thousands, if not millions of things that will kill them. If it were that easy, cancer would have ceased to have been a problem ages ago--Rest assured though, its not that simple.

Because a in vitro system excludes the complexity and systems of the whole organism, you never know if what you are cooking up in the lab will work in the body. There are hundreds of potential problems and limitations and most things that work in vitro don't work in vivo (I'm a link). They could require unachievable serum concentrations, they could be extremely toxic to another cell type, they could be metabolized or modified so as to be ineffective, they could lack the ability to hone to the particular cell type you want, they could only be useful on a target in a different body compartment than you are capable of delivering it too, etc

So when you hear claims about someone "killing cancer" and what a "great thing it will be"--You should be skeptical, because (like I put bluntly above), it doesn't mean anything in and of itself for reduction in human morbidity and mortality because of cancer. It is only a small, very small, microscopic even, first step on the road of designing and producing a clinically useful anti-cancer agent.

bobze

Some reading pleasure on "Rife cures";

Continue reading....

rhody

I have one question although complex, I am sure it will be vetted, is the technology of the day in the 1930's sufficient with Rife's insight and genius to be able to create a microscope as was claimed.

I have no agenda, am not a conspiracy theorist. Is the science behind Rife's microscope sound or not, and could it if were built as described have allowed him to view cells at the desired frequencies ?

Rhody...

atyy

@Rhody, I looked at some of the newpaper reports you linked to. I can't make head or tail of what was actually claimed.

The link you provide says the wavelength was 1/1000 of an inch ≈ 20 000 nm, which seems too large.

A light (400 nm -700 nm) microscope can resolve bacteria (>500 nm).
http://www.ruf.rice.edu/~bioslabs/me...icroscopy.html
"The smallest bacteria can be observed and cell shape recognized at a mere 100x magnification. They are invisible in bright field microscopes, though. These pages will describe types of optics that are used to obtain contrast"

Superresolution techniques improve things quite a bit.
http://zhuang.harvard.edu/
"Developing super-resolution optical microscopy that allows cell and tissue imaging with nanoscopic scale resolution"
http://optics.org/indepth/2/3/2
"Specifically, Fitzpatrick and the group of Salk Assistant Professor Clodagh O’Shea have been looking at how a small adenoviral protein spatially reorganizes DNA within a cell’s nucleus so that genetic programs which guard the cell against viral and tumor replication can no longer be activated."

Ygggdrasil

Well, if as you said in an earlier post, Rife's microscope used a crystal to pass polarized light into a microscope, then yes, the technology did exist in the 1930s. In fact, it existed 100 years earlier. In 1829, Williams Nicol invented the Nicol prism, a crystal that can be used to generate polarized light (https://en.wikipedia.org/wiki/Nicol_prism). Nicol prisms were commonly used in early implementations of polarized light microscopy.

However, Rife was certainly not, as you seem to be claiming, the first to invent a polarized light microscope. The first report of a polarized light microscope was circa 1834 (http://www.microscopyu.com/reference...35-55-2003.pdf).