

Study: Many pancreatic tumors are slow growing, taking 20 years to become lethal - cwan
http://www.hhmi.org/news/vogelstein20101027.html

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bhickey
I've only looked at the abstract (damn publishers), but superficially this
seems to be a great study. I'd just like to underscore how amazing their
samples are. The mean survival time of their patients, 2 years, is also
surprising. (Survival bias?)

Getting at metastases is hard. In general it simply isn't medically necessary
to biopsy them. Without medical necessity it's unjustifiable to put a patient
through that risk and discomfort. Why are metastases important? Mostly because
they're presumably cleaner than primary tumors.

In a primary tumor you start out some founder cell that has lost the ability
to undergo programmed cell death. In general, DNA repair mechanisms are also
awry. The cell divides producing daughter cells, the mutations add up and so
on. The tumor becomes heterogeneous. The daughter cells diverge from one
another. If you sample from the primary tumor you get plenty of mutations
related to cancer, and plenty of mutations _unrelated_ to cancer, simply
because the genome is a big place. It is no fun to work with this data.

OK. Metastases. Some immortalized cell has lost basal lamina adhesion and
migrated to another site in the body. This is a selective bottleneck -- all of
those randomly mutated cells that didn't lose adhesion are stuck in the
primary. The secondary should therefore be enriched for mutations in oncogenes
and tumor suppressors. This is why this data is so important and could give
some great insights into oncogenesis.

Heck, here's an experiment I would love to run:

* Collect biopsies from primary tumors in non-metastatic cases.

* Collect biopsies from metastases in another patient population.

* Look for mutations and changes in genome architecture that are unique/overrepresented in the metastatic cases.

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masklinn
Having lost my father to a pancreatic cancer, this is _excellent_ news. His
case doesn't seem to be an exception and it was utterly terrible (< 4 months
between the first symptoms and death). Pancreatic cancers are awful, and don't
get anywhere near enough attention.

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ubernostrum
Haven't had a chance to read the article yet, but I was under the impression
that the lethality of pancreatic cancer (and a few others) was mainly due to
the fact that it's so damned hard to identify _until_ it's beyond the point of
treatment. For example, during the period when the tumor is small, contained
and treatable, it (again, AFAIK) doesn't tend to manifest any symptoms, or the
symptoms which exist are identified as some other, more common issue.

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masklinn
> was mainly due to the fact that it's so damned hard to identify until it's
> beyond the point of treatment.

Yes indeed, which is why I talked about the first symptoms (though I could
have added the precision of the first _detected_ symptoms, in my father's case
a strong pain in the lower back for no apparent reason). According to the
article, pancreatic cancers are actually pretty slow and long-lived but they
tend not to make themselves known until the very end when they've already
started to metastasize and it's too late for treatment.

What I meant by "pancreatic cancers are awful" is mainly that the prognosis at
the moment is one of the worst possible.

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ben1040
Here's the paper in Nature for those who are interested.

[http://www.nature.com/nature/journal/v467/n7319/full/nature0...](http://www.nature.com/nature/journal/v467/n7319/full/nature09515.html)

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car
Great insight into tumor development. It reminded me of a scene in Dragon's
Egg, a Sci-Fi story about life on a neutron star, where the aliens cure a
female space travelers future breast cancer, by irradiating a tiny cluster of
mutated cells.

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noglorp
Great book!

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mey
Thanks for submitting this.

