
A cure for cancer: how to kill a killer - prostoalex
https://www.theguardian.com/science/2018/nov/04/a-cure-for-cancer-how-to-kill-a-killer-revolutionary-immune-system-immunotherapy
======
doctoring
I work in oncology and with some of the people interviewed in the article. I
want to emphasize just how exciting this stuff is and how wild it is to have
patients who have a belly full of innumerable metastases, for whom 5-10 years
ago we'd quote a few months' survival at best, and now on these new fancy
drugs their tumors just _disappear_. It's incredible and up until now
unimaginable for these late stage solid cancers. Similarly, to have people
with leukemias who previously we use essentially 40 year old drugs, now we can
fight and fight to keep alive long enough to get their T-cells harvested and
re-engineered and re-infused and then (after nursing them through a cytokine
storm) they emerge... with their cancer wiped out completely.

(The article blithely says "remissions measured not in extra weeks or months
of life, but in lifetimes". It's a little over-reaching since we just don't
have that much long term data yet; these therapies haven't been around for
"lifetimes". As a result we often prefer the term "durable remission" to
"cure".)

I also want to emphasize how _few_ patients have this outcome. It sucks. It
sucks to have ads on bus stops and TVs that say, "Ask your doctor about
Keytruda", but when they ask me, I know it has such a tiny chance of turning
them into that laughing family playing in the grass. We test for and hope for
the genetic markers that indicate certain immunotherapies are more likely to
work spectacularly, but the vast majority of patients don't have those
markers. Similarly, most patients with leukemias or lymphomas do not respond
to CAR-Ts.

We still try these immunotherapies, though, because there's often evidence of
some modest better outcomes, and also sometimes you get lucky. I think I
mentioned this on HN in some other context, but one of the breakthrough
discoveries around pembrolizumab was because of a "Hail Mary" in late stage
colorectal cancer; all the patients progressed & died in the study except for
one, and she held the key to the genetic derangement that made that subset of
cancer particularly sensitive to checkpoint blockade -- leading to FDA
approval for pembro for all cancers with that derangement. As this article
mentions, there is now a massive number of trials studying these therapies in
various subsets of patients, or in various combinations and permutations with
traditional therapy, because short of "cure" there's still improved survival
which can often be very meaningful.

It's exciting. It's inspiring. It's frustrating & heartbreaking.

~~~
wiz21c
In aother article pointed by the Guardian, I read :

>> Schmid said: “Immune therapy on top of standard chemotherapy prolonged
survival by ten months

Since, I guess, patient are interested by "being cured", how should I
interpret those ten additional months? Of course, I understand the statistic
behind it, but I' d like to know if it translates to something meaningful for
the life of the patient. For example, if I had a ten month increase in my
life, considering that it could mean live 10 month more with pain, false
hopes, etc., then I wouldn't feel that the situation has improved meaningfully
(of course I don't have cancer and therefore I may miss some obvious
benefits). OTOH, if that increase means that the chance of long time remission
also increase, then, that's a whole different situation...

~~~
chrisweekly
In my experience as a cancer survivor, it's all about "staying in the game".
Medicine doesn't change as fast as software, but extra months means a chance
to access new treatment options as they emerge.

~~~
resource0x
I'm another cancer survivor. My understanding is that you don't take this
treatment with the goal of surviving extra 10 month. You take in in the hope
to be cured, because they say there is a chance, however slim. So the rational
choice for me would be: take the treatment, and if in a couple of months it
proves ineffective, take euthanasia (if it's legally possible, which is the
case where I live - though probably there are still some unfortunate legal
caveats), Just hanging around longer would serve no purpose except increasing
the pain for my family. (That's my personal view only, not intended as a
template for anybody else)

------
darkerside
People seem to be disturbed by the indiscriminate nature of this cure. The
immune system, unleashed, will target not only cancer cells but healthy ones
as well. If this feels somehow aesthetically displeasing to you, ask yourself
whether it feels more or less clumsy to shoot radiation in your tumor's
general direction and literally poison yourself. Immunotherapy seems
positively elegant in comparison.

~~~
bsder
Um, actually, radiation is _MUCH_ better than most of the chemical options
unless you are one of the very fortunate few that has a particular receptor
than can be targeted.

Radiation has gotten _extremely_ good at being far more targeted. The doctors
actually model the absorption curves and let computers target the specific
areas to make sure that the specific area gets the necessary dose while
keeping the dose down in the surrounding tissue. If you can do radiation, it
is by _far_ the best option nowadays. Sadly, you can't always use it--sometime
surrounding tissue is too sensitive to radiation (intestines) and sometimes
things are simply too large.

Chemotherapy, though, just really, really, sucks. Almost anything is better.

~~~
darkerside
Yeah I hesitated at putting radiation therapy in there because I didn't know
how targeted it was. Thanks for an informative response.

------
ryanackley
Slightly off-topic but one thing that I've always been honestly curious about
is that literally billions of dollars are donated to cancer research each
year...but then the practical results of the research are sold to oncology
patients at bankrupting sums.

So my question is when we donate to cancer research, are we donating to public
research or are we handing our money to a for-profit corporation. What is the
path from donation to six figure cancer treatments? I would be very interested
in how that works.

~~~
Uberphallus
> the practical results of the research are sold to oncology patients at
> bankrupting sums.

In the US. [0]

[0] [https://www.healthsystemtracker.org/chart-collection/how-
do-...](https://www.healthsystemtracker.org/chart-collection/how-do-
healthcare-prices-and-use-in-the-u-s-compare-to-other-countries/#item-on-
average-other-wealthy-countries-spend-half-as-much-per-person-on-healthcare-
than-the-u-s)

~~~
kokey
The rest of the world can thank people in the US for spending rather large
sums on certain treatments. In the UK the treatments are covered by the state
at no cost to the patient, but it's only a limited set of available treatments
which are considered cost effective. In the US there are plenty more options,
if you can pay for it. People may decide to bankrupt themselves or sell their
house for these treatments that could enable them to survive or not, but
either way they are contributing to real world data that informs the rest of
the world of the efficiency and cost effectiveness of a particular treatment.

------
salex89
Not directly connected to the article, but the 40% chance of getting diagnosed
with cancer in my lifetime really sets of my anxiety...

~~~
nradov
If you live long enough you will eventually get some kind of cancer. This is
inevitable as DNA damage accumulates. Chances are something else will kill you
first, but detailed autopsies of older people frequently turn up small, slow-
growing cancer tumors.

~~~
philjohn
It's why at a certain age with Prostate cancer "watchful waiting" is often
preferable to invasive procedures. In some cases it will be so slow growing
you're likely to die of something else first.

------
yk
The article follows the standard convention of newspapers to hide any
qualifiers in the last few paragraphs, in particular the second to last
paragraph starts:

> Hype can be dangerous, just as false hope can be cruel.

I would therefore suggest reading the last two paragraphs carefully.

~~~
jm__87
They aren't hidden, they are just at the end of the article. To me this seems
like fairly honest reporting, as opposed to ommitting this info entirely.

------
tcbawo
The immune system is so complex, we can't even solve food allergies. We're
only scratching the surface, although I am hopeful for the future.

------
homero
I'm worried about these treatments for people with autoimmune diseases. One,
they might be on immunosuppressants, two, immune activation can then kill you
through the autoimmune disease.

I have ulcerative colitis and am on immunosuppressants. So I'm more likely to
get cancer and can't get that treatment.

~~~
doctoring
At our hospital we routinely use many of these therapies even in patients with
a variety of autoimmune conditions. In about a third of patients, they'll have
an exacerbation of their underlying autoimmune condition, which fortunately
only rarely necessitates cessation of the immunotherapy.

One of several studies we reference when we treat these patients:
[https://www.ncbi.nlm.nih.gov/pubmed?term=27687304](https://www.ncbi.nlm.nih.gov/pubmed?term=27687304)

What's interesting (and increasingly being studied) is the higher risk of
developing an autoimmune condition _after_ treatment with some of these
immunotherapies. The absolute risk doesn't seem to be huge, but it's an
interesting window into how these conditions might develop in the first place.

~~~
homero
That's good to hear. Would you stop, say Humira before treatment?

------
chopin
What the article unfortunately not explains: as far as I understand the
medication suppresses ways the immune system can identify healthy/own cells of
the body. If that is suppressed I'd expect more severe side effects, up to
death, no less. Why isn't this the case? Imho it could work only if cancerous
cells are more affected than healthy ones (like they are more affected by
cytostatic drugs because they divide faster). Can anyone chime in with an
explanation?

~~~
jcims
Some additional info here - [https://www.quora.com/How-does-PD-L1-checkpoint-
inhibition-s...](https://www.quora.com/How-does-PD-L1-checkpoint-inhibition-
selectively-target-cancer-cells-but-not-healthy-cells)

------
jobigoud
Pardon my naïveté. Has a honey-pot strategy been tried for Cancer? Like maybe
we can't kill it but we can lure it to develop in a very localized place, like
a cyst growing on the back of your hand or something, and then we remove the
cyst.

~~~
ryanwaggoner
Just as naive as you about this, but why would cancer developing in one place
mean that it can't develop somewhere else?

~~~
Udik
Ok, following with the totally naive speculation. What if it were not a place,
but a specific environmental factor or a specific trait? Cancers mutate
quickly, and resources are limited, so cells that are more successful might
starve those which lag behind, as it happens in animal populations. And once
the cancer has "fallen into the trap" of specializing for _something_ , that
something could be targeted, or the favouring environmental conditions
removed.

~~~
asdff
This is the clonal evolution model of cancer, and is how many solid tumors are
comprised and treated. The danger is that the selective advantage for the
cancer cell is often by masking itself as a healthy cell to the immune system,
which complicates treatments but this interaction can still be targeted (see
PD-1).

~~~
Udik
Yes, the idle speculation about a "honeypot" method was of artificially
encouraging the cancer to evolve in a certain direction, even boosting its
growth, until it has reliably mutated in a way that makes it susceptible to
some other intervention, like being starved or targeted by some particular
marker.

------
msiyer
I am honestly curious. What exactly is the root cause of cancer? The article
talks about cancerous cells tricking the immune system, but this trickery is
the result of something else. Immune system, in a healthy body, eliminates
cancer cells continuosly. What enables some cancer cells in some humans to
fool the immune system and multiply maliciously?

We can "manage" cancer without understanding the root cause. We cannot cure
it.

~~~
ufmace
AIUI, it isn't really a single disease with a specific cause. It's more like,
our body is composed of trillions of individual cells. Each cell is
theoretically an independent life form capable of doing its own thing. They
normally each have a program, encoded in their DNA, that keeps them operating
in service of the overall organism of our body - replicating only when needed,
dying when not needed, doing things useful to the body while they're alive,
etc. There's various environmental factors, radiation and chemicals and such,
constantly attacking that DNA. The DNA has self-repair mechanisms, plus the
body's defense mechanisms to kill badly behaving cells, so most mutations are
either repaired, ignored, or immediately fatal to the cell, kind of like
changing a random character in your program.

Over all of those trillions of cells and dozens of years, once in a while, a
particular cell gets just the right batch of random mutations that make it
possible to stay alive while breaking free of its programming and acting as
its own organism, independent of the body's plan. It may then proceed to
reproduce on its own, potentially disrupting the body's functions and/or
consuming all of its resources if it grows quickly enough.

So each individual cancer case is a uniquely evolved life form. There's a few
common threads that many tend to share, but no telling how many each
particular case may have. Thus, the broad brush approaches tend to be the most
successful - surgery, chemotherapy, and radiation. More directed genetic
approaches are tougher because of the uniqueness of each case.

Evolutionarily, it's a tricky balance. Too few mechanisms to keep all of your
cells under control all the time, and your body dissolves into a mess of
cancers too soon, like before you can reproduce. Too many mechanisms wastes
resources, can potentially go haywire and damage your body themselves, like
autoimmune diseases, or make it too hard for your body to evolve new and
useful adaptations to the environment. We already have good enough controls
that getting cancer before normal reproduction age is very rare. But now we're
living a lot longer, much longer than our bodies are evolutionarily adapted to
keep us alive for, so we see a lot more of these kinds of problems.

~~~
msiyer
I agree with most of what you say.

If living beyond the age we were designed for is the cause, I wonder why the
American Cancer Society says:

By 2030 the incidence rates among people ages 20 – 34 years will increase by
90% for colon cancer and by 124.2% for rectal cancer.

------
rishabhbits038
My dad had liver cancer which was detected early. We went with liver
transplant and 3 months later, cancer reoccurred in lymph nodes in his lungs.
Now, he's on immunosuppressants (tacrolimus and everolimus) for organ
rejection. Can immunotherapy still be tried on him?

------
kareldonk369
The cure for cancer already exists. We've had it for ages. It's THC found in
the cannabis plants. See research from, among others, Compultense University
in Spain.[1] Many people suffering from various forms of cancer have been
cured by using cannabis oil made from cannabis with high THC concentrations.

[1] [https://youtu.be/1miGzTwK28U](https://youtu.be/1miGzTwK28U)

------
jmcmichael
I've been working with a team* on an open-source analysis pipeline tool to
assist researchers and oncologists in identifying specific neoantigens used in
cancer immunotherapy. Given a patient's sequenced tumor/normal genome, it uses
a set of prediction algorithms and the public Immune Epitope Database to
produce candidate neoantigens for synthesizing the vaccines used in clinical
interventions or research.

We just released a browser-based client to assist users not comfortable with
constructing the long and complex command-line arguments used with most
bioinformatics analysis pipelines. It also provides a REST API that makes it
easier to integrate into existing research/clinical pipelines.

If you're working in this area of research/treatment please check it out to
see if pVACtools can be of use to you!

[http://pvactools.org](http://pvactools.org)

EDIT: Just received a writeup in GenomeWeb:

[https://www.genomeweb.com/informatics/wustl-software-
offers-...](https://www.genomeweb.com/informatics/wustl-software-offers-
automated-option-cancer-variant-review)

* as a user-interface designer/developer

~~~
aaavl2821
This is cool. Who is the main target user for this? Biotech companies?
Academic researchers?

~~~
jmcmichael
Both. It's currently being used mainly by academic researchers, and biotech
companies are evaluating it as well.

~~~
aaavl2821
How does it perform compared to any in house software at biotech companies? Or
are the main users companies that specialize in making cell therapies /
peptide vaccines and you just help them figure out which vaccines to make?

Am just interested bc i have a few friends involved in neoantigen / shared
tumor antigen cell therapy companies, and did some consulting work for a
company that had tech for delivering nucleic acid therapies and was
considering getting into oncology, but didnt have in-house sequencing or
antigen identification expertise. Mostly intellectual interest at this point

~~~
chrisamiller
The biggest difference between academic tools and those in industry is that
they're sinking major funds into producing (expensive, hard to produce at
scale) training data. That, in theory, should allow them to develop better
algorithms for actually predicting which mutations in the tumor are going to
be the best (immunogenic) targets. This tool, and several others like it, are
modular enough to allow you to plug in whatever prediction algorithm you like,
while still getting the benefit of all the other steps.

------
vectorEQ
killing things is bad mkay. prevent instead of cure. solve the root cause.

" “The tidal wave of data is still teaching us fundamental concepts about the
interaction of the human immune system and human cancer.” "

So, if they still learning fundamentals. -> impact of actions based on
inaccurate or incomplete knowledge, is unknown.

in programming this kind of practice would lead to bugs / undefined behaviour
etc. - imagine what kind of shit that would mean for human health...

It'd be nice if they had cancer prevention studies instead of cancer cure
studies. kthx

~~~
bananadonkey
When dealing with a software bug you have to reproduce the issue before you
can definitively "fix" it.

~~~
Koshkin
Not true. (It is often possible to understand the cause by just _looking at
the damn code._ )

~~~
barry-cotter
Humans, and every other life form have an undocumented, undesigned self
executing specification that consists entirely of the most reticulated, self
referential spaghetti code compatible with successful reproduction and it’s
not just riddled with Heisenbugs, they’re core parts of the machinery of how
everything works. We’ll get there eventually but it’s going to take an
exceedingly long time.

