
Drug made from toxic weed kills cancer - zio99
http://www.futurity.org/top-stories/drug-made-from-toxic-weed-kills-cancer/
======
tokenadult
I took care to read the fine submitted article (based on a press release) and
most of the preceding twenty-some comments before replying here. Comments to
the effect that we often see stories like this based on press releases that
don't translate into clinically useful treatments are correct. Anyone who has
been on Hacker News as long as I have has seen dozens upon dozens of stories
about breakthrough medical treatments that don't turn out to be breakthroughs.

As usual, here in this thread I recommend Peter Norvig's article "Warning
Signs in Experimental Design and Interpretation" about how to read research
reports in general.

<http://norvig.com/experiment-design.html>

Medical research is slow and painstaking. There has been genuine progress in
medical research in my lifetime. (My mother was a nurse in our state's largest
research hospital, and medical research was a subject of dinner table
conversation in my home.) But false starts have been numerous. There are a
great many medical treatments that have been proposed in my lifetime that have
not been proven to be both safe and effective for treating what they purport
to treat. Peter Norvig's article provides a good checklist of all the ways
that optimistic initial reports can turn out to be wrong, of which "too few
subjects" especially applies here.

I reply over and over and over again on threads like this here on Hacker News
because I did grow up with a strong interest in medical research--and some
anecdotes about medical research that went awry--and because I know that
legitimate medical researchers sometimes find their work hyped by the
university press office or funding agencies far beyond their own more cautious
statements. But here on Hacker News we may as well learn how to be discerning
readers. Let's not just believe what we want to believe, which is the
cognitive bias all human beings have, but let's test factual statements for
strong evidence and make sure that the experimental procedures reported in
some new study mentioned in a press release really support a grand conclusion.
It's too early here to say "Drug made from toxic weed kills cancer" in a way
that is safe and effective for a broad range of human patients for even the
one kind of cancer that is mentioned in the article submitted here. I'm glad
someone is working on this, but it's way too early to declare that we've found
a cancer cure through this work.

~~~
hef19898
Upvoted! What I really miss (in general, not just here) is a certain level-
headedness when it comes to things like this. I know it is hard to avoid the
hype since it is everywhere and omnipresent. but as technical people I still
want to believe that we can avoid it and think things through before we open
the champagne. We can do it in our own domains, why not in others too?

------
bedris
This study details the use of a peptide-drug conjugate; these are drugs with
peptides (small proteins) chemically conjugated to cytotoxic drugs.

The idea behind these conjugated drugs is that the peptide portion of the drug
hones in on a specific biological target and the conjugated cytotoxic drug
then kills the cells that have been recognized by the peptide (think warhead
and payload). In this case, the peptide recognized prostate-specific membrane
antigen, which is expressed on prostate cancer cells, and the cytotoxic drug
was one derived from _Thapsia garganica_ , the toxic weed (cytotoxic drugs
being isolated from plants is nothing new, of course).

A more common class of these conjugated therapies are called antibody-drug
conjugates[1], where an antibody molecule (instead of a peptide) is linked to
a cytotoxic drug. There is currently one of these drugs, Brentuximab vedotin,
FDA-approved for the treatment of cancer[2]. There are many more under
preclinical or clinical development.

[1] <http://en.wikipedia.org/wiki/Antibody-drug_conjugate> [2]
<http://en.wikipedia.org/wiki/Brentuximab_vedotin>

~~~
presidentender
So if prostate cancer has metastasized, and we target the cancer, do we do so
at the hazard of exposing the healthy prostate cells to the same fate?

Do the cells of other cancer-prone organs produce similarly specific antigens?

If so, how do we avoid the situation where we eliminate (for instance)
melanoma tumors of the brain and lungs only to have the patient's skin kill
itself off completely?

~~~
bedris
I think that all of your questions come down to two core concepts: therapeutic
index and antigen stability.

For therapeutic index, you want to identify and target antigens that show the
largest difference between cancerous tissues and normal tissues (i.e.,
antigens with a large therapeutic index). In other words, you'd want your drug
to bind to an antigen that's present at a higher level on the prostate cancer
cells than the normal prostate cells, such that the normal cells are spared.

For antigen stability, you ideally want your drug to target an antigen whose
expression is maintained in metastatic lesions. In other words, if a cancer
metastasizes from a primary site to a distant organ, and the antigen your drug
targets is maintained on the cancerous cells that have made their way to the
distant site, then that is a more therapeutically amenable target then one
whose expression is lost upon tumor metastasis.

Do those explanations answer your questions well? Let me know if you'd like me
to clarify more.

~~~
presidentender
The theraputic index explanation cleared my questions right up. Thanks!

------
rumblestrut
Sorry to sound skeptical, but back in the day cancer was killed twice a week
on Digg.

~~~
kintamanimatt
I really hate it when people express a predictable sentiment along the lines
of "herp derp, digg/reddit/HN cured cancer again! It must be Tuesday!" While
it's necessary to be reserved, scientific progress, especially in biomedical
fields should be celebrated, not derided.

We need more researchers in the world working on these problems that benefit
us all. Thinly veiled mockery of their work and the progress they're making is
really unsavory and possibly quite discouraging to someone who's thinking of
going into this field.

Just be grateful that progress _is_ being made; one day you may directly
benefit from that experimental drug mentioned in the article.

~~~
SoftwareMaven
The complaint is levied against the reporters, not the scientists. If we
actually heard from the scientists, we would generally get reserved statements
about progress and good indicators. That turns into a weekly cure for cancer
that doesn't really exist once we hit the "scientific" press.

In this case, it looks like the complaint is poorly founded. This is a real
breakthrough working on people cancer (as opposed to mouse cancer).

------
wkdown
ClinicalTrials.gov link [1]

Johns Hopkins link [2]

[1] <http://clinicaltrials.gov/ct2/show/NCT01056029> [2]
[http://www.hopkinsmedicine.org/kimmel_cancer_center/research...](http://www.hopkinsmedicine.org/kimmel_cancer_center/research_clinical_trials/clinical_trials/search_results/J09113)

~~~
rorrr
"This study is currently recruiting participants."

Well, get back to us when they find out all the side effects.

~~~
carbocation
That's like reading the announcement of new software and saying, get back to
us when they discover all the bugs.

Naturally, there will be adverse events due to toxicity. But unless you have
some particular insight into why this should be much worse in this case than
for other drugs, merely mentioning that there will be toxicities doesn't
really advance the discussion. At least, not as written.

~~~
rorrr
Do you realize that only 9% of drugs pass from Phase I of clinical trials to
the FDA approval?

Do you know why? Because the "cure" is worse than what they are supposed to
treat.

~~~
carbocation
Likewise, a small fraction of startups become successful.

Also, your allegation is wrong. Generally the reason for failure is not
adverse events, but lack of efficacy/effectiveness.

Will this likely fail? Yes. Will it likely fail due to adverse events? No.
Will it likely fail due to inefficacy/ineffectiveness? Yes.

------
traughber
I wish publications would wait for Phase 2 data before publishing
sensationalist headlines like this. In this case, they have yet to even
complete _enrollment_ for the Phase 1 trial.

~~~
refurb
I would wholeheartedly agree.

Most Phase I work is exploratory and things like statistical rigor and
blinding participants are ignored (and for good reason, those things don't
come cheap). Phase I data is useful for toxicity data, but I wouldn't trust
Phase I efficacy data in the least.

------
TomAnthony
To someone with a limited understanding of biology and chemistry, the logic
behind this sounds good and the initial results seem promising.

Yet, as people have commented, there are many similar stories that crop up.

Can anyone in the know shed some light on how often these things fail and at
what phase they normally do so?

Basically - how excited should I actually be?

~~~
robbiep
be cautiously optimistic. It's real research that has worked in animal models.
It remains to be seen whether it will be as effective in humans. Additionally,
shrinking a tumour is a long way from a cure.

For example - The drug Ipilimumab (melanoma) was shown in clinical trials to
increase median survival from 6.4 months to 10 months. Some people may have
disease-free recurrence for significantly longer than they would have, some
may actually be 'cured' (Disease-free survival for 5 years is a fairly
standard medical definition of 'cure'), others die at the same time, or a
week, or a month, later than they would have anyway.

For all of these drugs, there is no magic bullet, the tumour will evolve
around the mechanism.. My understanding of the subject (final year medical
student) has lead me to believe that an immunological approach will be best
(See my post which links to a nejm article further down the page)

hope this helps your understanding

~~~
cwjacklin
hey robbie, i am working on a crowd sourced site to find evidence based
treatment options for a disease. i would like to get feedback from you as you
are a med student. would you reach out? my contact is my uesrname at gmail

thanks.

------
EdwardTattsyrup
Shrinking tumors is good. It's also important to stop cancer from
metastasizing. I guess this drug might end up being used as a long term
"maintenance" therapy.

But I personally hope for a cancer therapy which goes beyond playing whack-a-
mole against tumors. Maybe one day they'll gain a more fundamental
understanding.

Maybe one day they'll actually know why the body begins to form these tumors,
why its built-in anti-cancer mechanisms fail or become overwhelmed, and, most
important, how to restore or unblock the body's own ability to control and
limit cancer cells.

~~~
robbiep
I don't think there is any great mystery there - mutation and copy errors
create the initial conditions that lead to loss of function of tumor supressor
genes or in of function in oncogenes, caused by known risk factors and some
unknown risk factors we are still elucidating.

There isn't a much more fundamental understanding that can be gained. We know
all of this, we are beginning to elucidate the chromosomal translocations and
karyotypes that seem to appear in certain families of cancers (and a specific
cancer type will have the same 'assortment' of chromosomal typings) all that
remains is to continue to design increasingly effective anti-cancer agents,
one part of which this article is explaining.

I don't believe there will be a single magic bullet, however treatments that
have an immunological basis (See this NEJM paper that offers incredible hope
for CLL - <http://dx.doi.org/10.1056/NEJMoa1103849> ) Or antibody based Rx
coupled to cytotoxics or radiologicals as an adjuvant Rx, as well as the
success of the designed molecules such as Imatinib etc all bode well for the
future. Unfortunately the big C will evolve it's way out of many of these
therapies (Imatinib etc inhibit fusion proteins created in aberrant cells that
lead to proliferation, slowing but not necessarily stopping growth, so the
cell evolves around it)

~~~
EdwardTattsyrup
But is there any hope that medicine will find a way to enhance or strengthen
any of the body's mechanisms for controlling these mutated cells and this
erroneously copied DNA?

Is that just a dead end?

~~~
robbiep
yes - sort of - that's what the paper is about essentially - it details a gene
therapy approach where T cells are removed, taught how to recognise surface
antigens for leukaemia cells and re-injected into the body, leading in 3 weeks
to a complete clearance of his CLL which he had had for 13 years and which was
close to killing him. Now THAT is a cure. So the immune system may be the key
to doing this.

but for what you are asking:

Things we can do now:

\- We can take things that lessen the chance of this damage occurring in the
first place (Anti-oxidants, good diet, 'everything in moderation', etc)

\- We can modify our lifestyle to avoid risk factors (Cut smoking, drinking,
drugs, bad food)

\- We can actively do things that are likely to strengthen our immune system
and the constant immuno-surveillance that it performs, that already stop us
from developing cancer at age 1 (Exercise, good sleep)

Things we Can't do:

: Because of lack of precedent, failure of mechanism, or lack of scientific
enabling principle (Your 'dead end')

\- We will probably NEVER (although that's a strong word in scientific
progress - let's say not for the foreseeable future, 25-30-40 years) be able
to take a pill that will REVERES the damage once it's done

\- We will probably NEVER (with the usual caveats) be able to take a 'simple'
drug molecule, as we understand the word to mean at the moment, to kill cancer
cells wherever they are in the body

: Because we just don't understand enough about how to do this:

\- We lack enough understanding to say what would happen if we were
potentially able to design a molecule that acted as a 'backup' to the main
TSP, p53, and were able to somehow deliver it into the cell to be a 'backup'
tumour suppressor and make the cell autodestruct if it got out of control

I could go on and on about theorised Rx'es, things we do now, things we are
just bringing online, and how I think it will all go down but that's probably
enough for a buried response in HN that few people will ever read. However if
you have any more specific questions or I can help you understand something
else, ask away

------
mcs
and we'll never hear about this again

~~~
ars
A while ago someone on HN suggested that whenever he reads about something
like this he creates an alert in google news for keywords, and then forgets
about it.

If anything comes of it, you'll get a notice.

------
johndavidback
If this drug also kills cells in near proximity to the cancer, would it be
effective treatment for brain tumors?

~~~
warfangle
The bigger problem with brain cancer is crossing the blood-brain barrier, no?

I don't think this molecule can do that.

~~~
robbiep
Brain cancers mostly disrupt the blood brain barrier, Which is an organised
tissue structure that exists to preserve the microenvironment of the brain
against normal fluctuations and insults. Cancer is disorganised tissue that
doesn't know how to produce nice neat blood brain barrier tissue organisation

~~~
bedris
Correct. This tumor-mediated disorganization of the blood-brain barrier (BBB)
is what enables cytotoxic drugs to reach larger cancerous brain lesions, which
explains why these growths often show a clinical response. Under normal
circumstances, many cytotoxic drugs cannot cross the BBB.

------
krollew
Nice to know, but I bet It won't be used widely soon, no matter if it works or
not. Medicine wants keep cancer pacients alive, not cure them. Curing is not
profitable. If they (and people themselves) wanted us not to be sick, almost
nobody would be.

~~~
ars
This again? It's nonsense.

Why do people believe garbage like this?

~~~
krollew
Because see how healthy man can be if only he want? Ever tried? Moreover
technology evolved so much and healthcare seams to work worse than before.
Think about it, science can tell what happens billions of killometers away and
what happens in subatomic scale and it can't find out how human body works
enough to cure most common diseases? It doesn't convince me.

And why not to believe? There are many people doing bad things. There are
wars, animals are treated like garbage. Why not to believe someone want to
make bussiness on disieses?

How about remissions, why nobody believe they occur for a reason? People are
too stupid to find out that reason? I don't think so. Or maybe am I wrong and
scientists try to find out why they happen?

Why basis of caring about health in mainstream medicine now are meds and
vaccination and not healthy diet and doing sports? I use no drugs and I don't
get sick. I used to, before i started to care what I eat and what I do for my
health. Noone ever told me to do what I've done. I rather seen commercials of
drugs that are not healthy and not realy work.

Does anyone care about that psychedelic drugs relieve cluster headaches (where
no other good working med is known)? Anyone cares MDMA decreases symptoms of
Parcinson disease? Is it so difficult to find out why? I mean, if anybody
except single scientists care? I don't mention how great can they impact on
state of mind.

Hemp is great painkiller, medicine for insomnia, and others. Why I can't use
it to relieve my pain or to help myself fall asleep? Why medicine use much
more dangerous drugs if hemp could be used? As far as I know It's illegal
because someone don't want to admit it's useful for medical reasons.

Medicine is so broken. For me someone want it to be broken or people in
medicine are stupid. I can hardly believe they are so stupid so I'd rather
believe second option. The fact that some people always wanted to enslave
somehow other people. We had explicit enslavement and religion. Why medicine
wouldn't be next one?

~~~
ars
You assume people are doing this for "bad reasons". Or to make money.

It's not so. Medicine just doesn't know any better.

Each year they get better and better, but overall they barely know anything.

The body is VERY complicated, and people just don't understand it very well.

You think someone "cured" cancer but did not sell it to make extra money. Not
so - there are so many people with cancer that they would make a HUGE amount
of money by curing them all. And there are new cases all the time.

Remember that even the most profitable drug it's only for 20 years, then is
not protected anymore.

20 years is plenty of time to make lots of money.

~~~
krollew
Yeah, but if no drug is not realy needed, you can't earn on it. Groceries and
gyms does. Sorry, change of lifestyle made very big impact on my health. My
immune system works so well cold can't become enough serious even to make me
feel bad. I practicaly don't get sick. Moreover I noticed mood lift, better
work of brain, no insomnia anymore, I have much more energy.

My body seems to know what is good for it - it prefers healthy food and don't
accept stuff are not healthy. It even doesn't want beer anymore. ;) Why the
hell nobody told me about that? If science made reserch on that, no flu
vaccination or pro-immune drugs would be needed! Even more - there would be
less cancers, heart diseases and so on. Nobody deny diet has big impact on
those disieses, but noone what to use it. THEY KNOW how to do better, THEY
DON'T!

And I'm not the only one. I know guy who treated asthma and alergy, which is
in fact possible, in some cases, but no doctor even tried to do that.

And since he found information how to do that and I did - surely there are far
more people does better than mainstream medicine. Think about it, some regular
guys with no medical knowledge does better then proffesional doctors. Doesn't
that mean there's something wrong with healthcare? Is there realy no reason to
be sceptical about how it works?

~~~
FreebytesSector
The profits for a drug to cure every kind of cancer would be astronomical. You
seem to have the assumption that when cancer is killed it cannot return. But,
it can. Mutations happen often and because of this, cancer would happen often.
Cancer kills people. You do not want your customers to die. It would be more
profitable to release a cure and have people take it whenever cancer is found
because it is certain to return.

You mentioned that changing your lifestyle has made you healthier, but that
has been mentioned to me by my doctor every time I visit! Eat healthy, get
plenty of rest, and exercise. We have heard this many times before. This is
not some magical secret to a healthy life. Many people simply do not possess
the willpower to do it. There are companies that profit from unhealthy choices
because our bodies crave those unhealthy choices, but it does not mean there
is some conspiracy by scientists to prevent drugs from reaching the market
that can cure cancer.

The cure would be more profitable because over a long enough time line, cancer
returns. People that get cancer are often predisposed to getting it in the
first place.

~~~
krollew
Well, I won't argue any longer if cure for cancer would be more profitable or
not. I'd need some professional analysis. I'm not proffesional so I don't
know. Anyway they already take much money for treatments that doesn't realy
work. It's quite good bussines. For sure it's very easy and safe strategy to
keep status quo. What if cause of cancer would be found and it would no longer
come back after treatment? Working cure wouldn't be so profitable then.

Yes. I wrote that everybody know that people should live healthier. But there
is big problem. Telling is not enough. How people who never had proper
lifestyle and diet can know what "healthy" realy mean? They only can assume
that if they feel like they felt before they are healthy. Maybe not perfectly,
but they are. This assumption is simply wrong.

Do you know people who live healthy? It seems to be highly addictive and
spread quite fast. The only condition is that people have to see that those
one who live healthy are far more healthy than they ever asumed. For example
one of my frieds i live with in one flat needed only few weeks of watching how
do I eat to decide to improve his diet. He's happy he did that. He loves
oatmeal for breakfest too (also my habit). I doubt if someone who live healthy
would like to stop. If you go to doctor you don't see what to expect so you
don't change anyhting.

