
Woman’s cancer killed by measles virus in trial - arunpjohny
http://www.washingtonpost.com/news/morning-mix/wp/2014/05/15/womans-cancer-killed-by-measles-virus-in-unprecedented-trial/?tid=hp_mm
======
zaroth
Oncological Virus, or OV. Pushing science fiction. But did Washington Post
forget to mention the 2nd patient they released data on, who didn't have any
kind of prolonged response?

The paper presents 2 cases, selected because they were the first 2 cases to be
tested at maximum viral load. There are additional people in the trial, and
they will release full results once they are available.

It included two slides showing before/after blood levels and imaging. They
talk about how they modified the virus to emit a tracking signal, and how they
modified it to target the cancer cells. Really, really mind blowing and
impressive work. I would _love_ a tour of that lab.

These are end-stage patients for whom everything else has stopped working. One
of the patients had already undergone several experimental treatments. There
is some really exciting research going on for MM (multiple myeloma)
treatments, and maybe even cures.

I think this is one example of the free market working well. Typical MM
treatment runs about $60k / year, and with recent developments, patients are
living 10+ years. Total number of MM patients is increasing both because the
disease is becoming more prevalent, but mostly because people are living so
much longer with MM. In short, it's a large and growing market. But it's not a
cancer you can treat and have it go into remission. You get on treatment, and
you stay on it and keep those levels down. The typical treatment is biweekly
therapy.

But these OVs are one-time deals. So a single dose treatment is a very
interesting alternative. The only problem is, MM is extremely resilient, and
the cells are _everywhere_. It's so hard to eradicate, unless the OV is a
cure, it's just another tool in the box to _manage_ MM and extend lives.

Weird, the PDF of the actual paper was freely downloadable a couple hours ago,
but now it seems the paywall is up?
[http://www.sciencedirect.com/science/article/pii/S0025619614...](http://www.sciencedirect.com/science/article/pii/S0025619614003322)

~~~
ekianjo
> But these OVs are one-time deals. So a single dose treatment is a very
> interesting alternative. The only problem is, MM is extremely resilient, and
> the cells are everywhere. It's so hard to eradicate, unless the OV is a
> cure, it's just another tool in the box to manage MM and extend lives.

Yes, the key point to watch next is to see if the MM does not come back after
a couple of years.

~~~
im3w1l
One thing I don't understand is this attitude of "well we can't detect it, so
job is done". I don't know the specifics of detectability, but presumably it
means that n<N for some N. So there could still be some cells left. Why not
throw every weapon in the arsenal at them, to ensure the cancer is completely
gone?

EDIT, addendum: If you have a few treatments that each can kill 9999/10000
cancer cells. It seems the current approach is apply treatment a. Not
detectable yay! They grow back to original numbers. Apply treatment b! etc. If
you did them all at once, they wouldn't have time to grow back in-between
treatments giving a larger chance you get them all.

~~~
mrfusion
Great question. I've wondered the same thing for bacterial infections.
Wouldn't it lower the risk of resistant bacteria developing to always use two
different types of anti-biotics, so in case a few bacteria develop a
resistance to one, they're still killed by the other.

~~~
DaveWalk
This is much easier for bacterial infections vs cancer -- chemotherapy is
(excuse the non-medical phrase) very close to actual poison. Antibiotics are
very well-tolerated, so taking two at once is something that could be done and
is indeed deployed in serious infections or when there is high risk of one.

~~~
Fomite
This - nearly all antibiotics target parts of the bacterial cell that humans
don't have. Antifungals have the problem that many of their targets are shared
between eukaryotic fungal cells and our own. Chemotherapy agents have a _huge_
problem in that they are targeting cells that used to be our own. It's a race
between toxic to cancer cells and toxic to the rest of you.

------
lifeisstillgood
OK, this is a silly question but I have to ask

Is there any likelihood that measles, or a similar virus we have held at bay
with vaccination, was actively fighting cancer 200 years ago, thus pushing up
the incident rates that apparently have gone up and dismissed with "well we
weren't dying of cancer because we were dying of $INSERT_DISEASE_HERE"

~~~
has2k1
It is not a silly question. We can put it through the paces. The question you
are getting at is, "Did measles evolve to keep cancer at bay?" Or stated in
another way, "Did it evolve because it was keeping cancer at bay?" The 2nd
question is more attuned to our understanding of evolution.

For this to be the case, cancer must have been killing a significant number of
people before they reached the reproductive age. However, we know cancer rears
it's face well passed people have reached reproductive age. For women, breast
cancer the most common of them all becomes rampant post-menopause.

With this view point, it seems unlikely that measles was an evolved response
to cancer. Because, this has been a hand waving argument it has not addressed
the ratios required for an evolutionary response, i.e Is it possible that
cancer was killing enough (however small) prepubescents and that gave measles
a chance to evolve?

Or, could it be that there was a way milder measles like virus that people
acquired (like the common cold virus) and lived with henceforth and that
protected them from cancer?

There are many interesting questions that come up.

~~~
tdaltonc
The viruses didn't have to evolve specifically to fight, it could have been a
side effect. For example, maybe cancer cells make better viral hosts because
of their unchecked metabolism. So the virus evolves to exploit cancer cells
first, killing them in the process. Here the virus "cures" cancer by accident,
with no interest in the fact that it extends the life of their host.

I'm not saying this is likely, I'm just pointing out that your restatement of
the question is a lot more narrow than the original question.

~~~
has2k1
That was by intention. Head on, the original question is less penetrable. The
restatement is meant to emphasize that a symbiotic relationship between the
host and the virus could drive the evolution. Cancer -- bad for host, virus
takes care of cancer for selfish reason, host lives long giving virus
opportunity to spread. Along this line, your example gives a possible
immediate attraction for the virus. It is the immediate attractions that start
off the relationships, to disastrous, neutral or beneficial long term ends.

It is even possible that different viruses could be fighting each other to get
a piece of our cancer. Interesting stuff!

~~~
lifeisstillgood
Ask a dumb question, get a great thread out of it.

Thanks

------
darkFunction
I am curious about the timescale of treatments for terminal diseases, and how
trials can be morally randomised.

It seems to me that a very high percentage of people would opt for a
potentially fatal, completely untested course of action as opposed to imminent
death. So who gets to try these treatments, who tells dying patients they are
not allowed them, and is there a black market or large amounts of money
changing hands for experimental procedures?

Ekianjo in this thread quoted 7 years at the earliest for a treatment to
become available. Surely with hundreds of thousands of desperate, dying, last
chance sufferers, it is better to go to extreme measures and offer the most
promising yet dangerous treatments to everyone. Is it simply a side effect of
the way pharmaceutical companies have to do business? If so, it's sad, and
maybe a larger share of cancer research money should be put towards 'out
there' attempts to cure terminal patients.

Genuinely curious.

~~~
zacinbusiness
It's valid morally. However, science runs on grant money and grant money will
usually only be given to projects that show a proper scientific method. It
would be nice if there were some sort of open market, where terminally ill
patients could opt in to clinical trials. But these trials must be tightly
controlled, or their results are meaningless.

~~~
darkFunction
I would argue that as a terminal patient, I certainly would not want to be
part of the control group taking a placebo or no treatment at all, and that
the scientific method could still be applied _later_ when you still have a lot
of people that took the treatment compared to a lot of people who didn't, for
one reason or another. I imagine scientific grants could be funded on an
individual basis, if the individual is rich enough.

~~~
ekianjo
Usualy placebo arms get less than 50% of the patients anyway. So most people
on trials get the drug. And no, you cannot "apply the science later" because
you specifically want to see the difference in PFS (progression free survival)
and OS (overall survival) on both groups, and for it to be comparable they
need to start with the same baseline.

~~~
phkahler
But we're talking about people who have been told "this disease is going to
kill you." If a treatment causes even 5 percent of them to be cured, how is
that not significant? What if 40 percent have tumors shrink? Remember, any
reversal of the disease is a good thing. If you're just measuring a
statistical increase in life span (say 3 years treated vs 1 year placebo), I'd
say you're not really aiming high enough. If you've got something with real
promise you'd know it without a control group. The person in this article is
exactly such a case.

~~~
zacinbusiness
It's more that the controlled placebo group will also be controlled for other
medications that could compromise the research. If I have cancer A and I'm
taking three or four medications + an experimental medication then it's
difficult to know which factor affects the results. So the control group will
be on the same types of medication in a proper study where as a sort of ad-hoc
grouping of patients would be less easy if not impossible to accurately
report.

~~~
phkahler
I assumed we'd be comparing to the predicted outcome from no treatment, but I
suppose if you wait until Hospice time there's not going to be much success
with even the best virus compared to doing nothing. Which raises other
questions about just how long and at what cost we try to delay the inevitable.

------
bambax
Is this real? Can anyone with actual knowledge of the history of fighting
cancer with modified virus provide input?

From my completely uninformed point of view it seems that if it's real, it
changes everything...

~~~
SeanDav
I see no reason why it isn't real, unfortunately a trial of 1 does not a cure
make, however it does seem very hopeful, even if there is a long way to go
with more extensive trials.

~~~
ekianjo
Indeed. We see these kind of n=1 reports every now and then and media jump on
the hype gun without understanding drug development at all.

------
baldfat
Cancer = Worst word for multitude of diseases where most are not related to
each other except cell growth. Wish they could just not use it anymore.

Dad of a child who died from cancer and well the word cancer doesn't mean
squat you need to know what type of cancer. Is it sarcoma or what?
[http://www.cancer.gov/cancertopics/types/commoncancers](http://www.cancer.gov/cancertopics/types/commoncancers)

~~~
nkozyra
I think this is unfair - obviously each type of cancer has unique properties
but the general ontology, mode of operation and treatment options have enough
overlap that it - in a single word - describes what an illness is in general.

~~~
gus_massa
“Cancer” is a very wide classification. It’s similar to classify the illness
as “caused by bacteria” or “caused by virus”.

It’s not very useful to know only that you have a disease that is caused by a
virus. It could be a common flu, melease, ebola, herpes, hepatitis, hiv, ...
[http://es.wikipedia.org/wiki/Virus#mediaviewer/Archivo:Viral...](http://es.wikipedia.org/wiki/Virus#mediaviewer/Archivo:Viral_infections_and_involved_species.png).
Each one has a very different treatment and prognosis.

Some cancer would kill you in a month and some will kill you in 100 years (if
you don’t die from other cause), some cancers are easy to operate, some are
easy targets to chemotherapy, some for hormone therapy, some for radiation,
... A cancer diagnosis is a bad new, but it’s a very wide range of bad.

Also a new “cure” will probably be useful in a very few specific cases, and
not useful in a general case like a broad spectrum antibiotic, that is useful
against a lot of kind of bacteria.

~~~
nkozyra
Except that bacterial and viral infections have a disparate set of effect with
no guarantee of any overlap beyond "disease."

Such is not the case with cancer. Prognosis is the main differentiator, but
that's not enough to say "stop using cancer as a catch-all."

It's a wide classification that _still tells you what is happening inside the
body_ , which is not the case with a bacterial or viral infection.

------
Gatsky
Phase III study of virotherapy here (not published yet):

[http://www.marketwatch.com/story/amgen-provides-update-on-
ph...](http://www.marketwatch.com/story/amgen-provides-update-on-
phase-3-study-of-talimogene-laherparepvec-in-patients-with-metastatic-
melanoma-2014-04-04)

[http://en.wikipedia.org/wiki/Talimogene_laherparepvec](http://en.wikipedia.org/wiki/Talimogene_laherparepvec)

Not, it would seem, a panacea. Approach is interesting in that aspects of
cancer biology make the cells more vulnerable to viral infection, eg supressed
interferon production. Also a possible platform for immunotherapy ie getting
the immune system to attack a virally infected cancer cell might wake up a
more generalised immune response. But, medical grade virus is expensive to
produce, and hard to think how a viral infection could eradicate 100% of the
billions of cancer cells present in advanced disease. Also, humans get immune
to viruses after infection.

------
nabla9
Using virus infections against cancer has long history.

[https://en.wikipedia.org/wiki/Oncolytic_virus](https://en.wikipedia.org/wiki/Oncolytic_virus)

~~~
phkahler
And a long history of not becoming wide spread. From TFA "Russell said he and
his team had engineered the virus to make it more suitable for cancer
therapy." I just assumed the term "suitable" really meant "profitable" but
some of the comments indicate it was modified to target the cancer better (how
so?). It seems the cost of trials and approvals is too high for a naturally
occurring virus, so everyone wants to customize them so they become
patentable.

~~~
zaroth
The naturally occurring virus would not treat MM. There is real R&D going on
here to make this work as an MM treatment.

From the paper: "Unlike naturally occurring measles, MV-Edm, and hence MV-NIS,
targets CD46 as a cell-entry and cell fusion receptor. CD46 is a ubiquitous
complement regulatory protein that, fortuitously, is highly expressed on human
myeloma cells, making them abnormally susceptible to MV-NIS infection,
syncytium formation, and cell killing."

So they tweaked the virus to target CD46 which MM cells express way above
normal. The MM cells are therefore significantly more susceptible to being
killed by the virus.

------
NKCSS
I am always happy to see advances in treating cancer. Lost my dad to cancer a
few years ago, it would be great if people in the future have a better chance.
I know there will always be new diseases, but nipping this one in the bud
would be awesome.

~~~
ekianjo
Very sorry for your loss :(

I might add there's no such thing as "cancer", cancer is caused by numerous
kind of mutations (from various origins, including viral infections) and
there's no single bullet against cancer. There are already many good
treatments for several types of Cancer but not all, and cancers discovered
late have usually bad prognosis no matter what. This being said there are
exciting new treatments coming in the 2010s using antibodies instead of
regular chemotherapy, which may improve survival for many patients.

~~~
josephagoss
I don't know much about cancer, but it seems like a common denominator is that
they are all forms of unregulated cell growth.

Doesn't that mean there is such a thing as cancer? Perhaps the final cure
would be an augmented immune system that can tunnel to any area of the body
and remove these cells. Something like nanobots I guess.

Although I do understand your point, that the several hundred forms of cancer
in humans require radically different approaches for curing until nanobots.

------
ck425
From what the article says I think the original virus works by attacking
tumors which then explode and spread the virus all around the body. If they
use a version of the virus that is safe or that the person is immune to then
it would target the cancer and cause it to explode but afterwards be harmless.

That's just the impression I get from the article. I know literally nothing
about this do if anyone with actual knowledge can explain properly please do!

~~~
goblin89
(I also know nothing about this stuff.) From the article I gathered that, if
the person is immune to this anti-cancer virus, it won't have any chance to do
its job before it gets eradicated from the system. Which seems to be a
problem: after first attempt this treatment won't work again since one's
immune system will definitely recognize the virus (having immune system
weakened might do the trick though).

The article also mentions that most people in US are vaccinated—I'm not sure
how to read that: vaccinated from this particular virus?

------
cromulent
The immune system is so complex that this is difficult to understand. I
imagine there is some link to the Abscopal effect, where radiation treatment
of one tumor in one part of the body kills the other metastatic tumors.

[http://en.wikipedia.org/wiki/Abscopal_effect](http://en.wikipedia.org/wiki/Abscopal_effect)

------
Stately
This is too similar to how I Am Legend begins.

~~~
LeonM
Your comment is downvoted, but I had the exact same thought.

What are the long-term risks if we start injecting people with large
quantities of a virus to battle another decease? Could that virus evolve into
something much worse than cancer?

~~~
kennywinker
It's not the injecting large quantities of virus that poses a risk, it's
genetically modifying viruses and then exposing people to them that is risky.

I would hope that quarantine procedures around any human made-or-modified
virus would be quite strict to avoid something unwanted making it's out of the
lab.

------
anon4
_Currently, there are no do-overs since the body’s immune system will
recognize the virus and attack it_

Can't they circumvent this by injecting more of the virus than the body can
fight at once? Though it's starting to sound like regular expressions...

~~~
sounds
The immune response might be fatal – anaphylactic shock.

------
majkinetor
Nobody underlined that woman got very high temperature. It could be the reason
for the results. Coley's toxins were used century ago for that effect. In fact
Sensei Mirai clinick in Japan recently reported remission of ~370 terminal
cancer patients using combination of immunotherapy and high dose vitamin C &
D, along with termotherapy. Cancer patients usually didnt have temperature
long time before diagnosed.

[http://en.wikipedia.org/wiki/Coley's_toxins](http://en.wikipedia.org/wiki/Coley's_toxins)

------
programmer_dude
Yay for science! Though I am not quite sure why the virus only attacks
cancerous cells. Has it been modified to identify cancer cells?

~~~
anonymfus
_> Two patients in the study received a single intravenous dose of an_
engineered _measles virus (MV-NIS) that is selectively toxic to myeloma plasma
cells. Both patients responded, showing reduction of both bone marrow cancer
and myeloma protein. One patient, a 49-year-old woman, experienced complete
remission of myeloma and has been clear of the disease for over six months._

From the link mentioned in "According the clinic’s statement released
Wednesday" line.

------
zenbuzzfizz
I don't see any discussion of the M-count (monoclonal protein) response. My
understanding is this is the key measure of myeloma.

It would be really great if this turns out to be a real treatment option
because, harsh as it appears from the article, this woman's treatment sounds
way easier than the current therapies for myeloma.

------
j_s
Thought this was the same as discussed 2 weeks ago, but that was polio going
after a brain tumor:
[https://news.ycombinator.com/item?id=7686853](https://news.ycombinator.com/item?id=7686853)

------
kevin818
Anyone else worried that using virotherapy may result in those virus' building
up resistance, similar to what's happening now with antibiotics and superbugs.

~~~
Fomite
Resistance to what? There's no particular selective pressure on the virus.

If you mean the _cancers_ becoming resistant, one of the appeals of using
viruses in therapeutic settings is they can evolve right alongside their
targets, helping mitigate some of those resistance problems.

~~~
kevin818
Apologies, I was referring to the cancer becoming immune.

------
svyft
Some indian ayurveda recipes use poison to cure poison.

~~~
kennywinker
Some indian ayurveda recipes use heavy metals to cure diabetes. They don't
succeed, but they do cause heavy metal poisoning.

[http://www.bcmj.org/bc-centre-disease-control/heavy-metal-
po...](http://www.bcmj.org/bc-centre-disease-control/heavy-metal-poisoning-
ayurvedic-medicines)

------
jameshk
This is progress! Happy to see some success!

