

Cancer’s Super-Survivors: How Immunotherapy Is Transforming Oncology - larrys
http://online.wsj.com/articles/cancers-super-survivors-how-immunotherapy-is-transforming-oncology-1417714379

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tokenadult
The article reports, "Most experts believe it will take combinations of
immunotherapy drugs—or combinations of immunotherapy with other cancer
treatments—to optimize their impact. But finding safe and effective
combinations is a daunting undertaking." Yes. A lot of researchers, including
researchers at companies that could commercialize applications of the latest
research findings, are working on the general approach described in this
interesting article, because the approach, if refined, promises substantial
increase in healthy lifespan for many patients diagnosed with cancer. Making
each patient's own immune system more responsive to cancerous cells looks like
an important part of further advancing cancer treatment.

A key idea in medical treatment research is to look for an "endpoint" that
actually matters for the patient. When the researchers looked for tumor
shrinkage, they sometimes didn't find it soon enough to think that the
patients were benefitting from treatment, but the patient Tom Telford named in
the story reported feeling better during treatment, even when his tumor still
appeared to be huge on scans of the tumor. When the researchers looked for the
"hard endpoint" of patient survival, they found out these new treatments are
better than they had realized at first. Proxy endpoints never beat hard
endpoints in evaluating a treatment.

One more comment about how the story is presented. I will be really glad when
doctors speaking to reporters, who are trying to talk in conversational,
understandable language, and the reporters themselves get out of the habit of
personifying or anthropomorphizing cancer cells, immune system cells, tumors,
or even autonomous human body functions. Cancer cells and immune system cells
are not knowing agents. They adapt (that is, successful cells survive while
others die) but they don't "learn."

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autokad
its not a big deal, your just caught up in language. in a sense learning is
just adapting, 'successful' neurons propagate, less successful ones wither.
also its helpful when thinking about these things to not fall for the fallacy
that cancer and the immune system is simply cells - they are complex systems.
For instance, the immune system does learn and adapt.

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musername
learning is a directed process with a target. the immune system is controled
by the bervous system to reach that target, while cancer-cells, apparently are
uncontrolled. there's a difference, although it matters more in an educational
context.

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salgernon
Is there any indication that these treatments can help is prevention or return
of metastatic rumors? (As someone going through treatment for stage iv colon
cancer with liver metastasis. The erbitux has done wonders in shrinking the
tumors, but there are serious skin toxicity issues that may require me to
change regimes.)

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dnautics
OK. I am not a doctor (just a PhD biochemistry)

I think that currently with these treatments complete remission is luck of the
draw. Although many of these treatments (trastuzumab, cetuximab) were designed
to block a growth factor from signalling on the cancer, what they ALSO seem to
do is to recruit the immune system to the cancer and basically paint the
cancer with a giant target.

Now, there is basically a competititon here; is your immune system powerful
enough to kill the cancers painted by the antibodies faster than the cancer
can adapt (usually by short-circuiting the growth signal). This sounds hokey,
but for patients on these class of antibodies (ADCCs "antibody-directed, cell-
mediated cytotoxicity"), I'd say it's important to keep a positive attitude,
eliminate stress from one's life, and other things that strengthen the immune
system. Unfortunately there are a lot of chemotherapeutics which are
coadministered with these antibodies that throw a wrench into the immune
system, as does radiation, etc.

As for the future, I think that there are some sneaky tricks that we can do to
make ADCC drugs more powerful. Right now there is actually batch-to-batch
variation in the power of these drugs, again going back to the 'luck of the
draw'.

I also see some potential for ADC ("antibody-drug conjugate", not to be
confused with ADCC) as well, this is attaching a warhead to an antibody and
just directly killing the cells, although I think the ADCs that are being
designed _are not potent enough_. But that is another story.

Finally, there will be a class of general chemotherapeutics that don't touch
the immune system (I work on one through my nonprofit, there is one in Phase
III - SJG-136) which I think will make for a nice 'sweeper' system to clean up
any cells that have snuck out of whatever the antibody target is.

In short: I see a future where ADCCs are combined with ADCs and next-
generation chemotherapeutics.

The other big challenge is that it's kind of very expensive to make antibody
drugs. I think there are clever ways of bringing the cost down, and I might be
working on that too.

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jreed91
This article hits close to home as my father had stage IV melanoma and took 2
rounds of Yervoy before becoming too sick and eventually passed away earlier
this year. These drugs are very promising but the costs are absolutely
ridiculous. $120,000 for four rounds (which is the initial amount you get
before you must wait to complete more) is not viable for most people. Lucky my
father has terrific insurance we paid maybe 10% of that cost. I did a lot of
research on these drugs and there are some very severe side effects that you
must watch out for. For most people these drugs are only slowing down the
spread of the disease but by combining yervoy with other chemo drugs it can be
very effective at treating melanoma.

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hga
_but the costs are absolutely ridiculous. $120,000 for four rounds..._

As the article details, it took 15 years to bring this drug to market, and the
process has been and continues to be very research intensive. That money also
pays for failures, it's not cheap to produce, and it's sold in small
quantities for a currently small number of patients.

Yeah, it's not wonderful, but every time I hear that sort of thing, I also
hear the sentiments that are (not so?) slowly shutting down new drug
development.

You'll see this play out rather starkly as bacteria become continue to become
more resistant to the usual antibiotics.

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esturk
Just today, an early release in the finding of the immunotherapy drug
nivolumab being use to treat non-Hodgkin's Lymphoma shows over 10% (4/29) of
patients in complete remission. So I say that's pretty good. Dr. James Allison
even said that for the 20-25% of patient that get an everlasting remission
with Yervoy, that's great.

And those numbers will only go up.

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byteCoder
Immunotherapy absolutely works for melanoma–I'm living proof. As a Stage IV
melanoma survivor, immunotherapy via a tumor infiltrating lymphocytes (TIL)
trial at NIH has extended (if not saved) my life. I'm over two years out from
treatment and am currently NED (no evidence of disease).

Also, Federally-funded research at NIH continues to push the envelope at
relegating cancer to a chronic disease (if not cured altogether).

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delinquentme
“Death is not an option,” he told his doctor.

~~~
niels_olson
There's only one thing you have to do in life. Any you don't have to pay
taxes.

~~~
gomerclaus
Your defeatism is unbecoming.

