Protein Converts Pancreatic Cancer Cells Back Into Healthy Cells

An anonymous reader writes: Scientists working in the area of pancreatic cancer research have uncovered a technique that sees cancerous cells transform back into normal healthy cells. The method relies in the introduction of a protein called E47, which bonds with particular DNA sequences and reverts the cells back to their original state. The study (abstract) was a collaboration between researchers at the Sanford-Burnham Medical Research Institute, University of California San Diego and Purdue University. The scientists are hopeful that it could help combat the deadly disease in humans.

Comments

Cancer vs common cold

[ArcadeMan]

I bet we find a cure for all kinds of cancers before we find a cure for the common cold.

Re:Cancer vs common cold

[Misagon]

The problem is that neither cancer nor cold are of "common" types: there are quite a few types of each.
One man's cancer could be quite different from another man's, even if they are both found at the same place in the body. The pancreatic cancer mentioned in the article is only one type of pancreatic cancer, although it is the most common form that would originally form there. Cancer in the pancreas could also be another type of cancer that was formed elsewhere and metastasized.
Similarly, there are many different viruses that can cause "cold".

Re:Cancer vs common cold

[ChadSmith4920]

It's a step in the right direction. Perhaps other 'TYPES' of these proteins could be matched to other 'TYPES' of cancer cells.

Re:Cancer vs common cold

[Anonymous Coward]

Unlikely. The common cold is a collection of well known rhinoviruses -- a very specific virus and we have quite a few anti-viral and inoculations against viruses. Cancer on the other hand, is the cell division process gone amok and it can happen in many different ways for each cell. If by "kind of cancer" you mean one of the many ways it can run amok then, maybe we will find cures for individual kinds of cancer. Unfortunately that doesn't mean we have cured cancer or even cancer of a specific organ system.

While this is a breakthrough in cell modification, turning that into an actual cancer treatment is a long way off. It wasn't just "introduction" of E47 it was induction of that cancer cell line to produce more E47. So, there are concerns of safe gene therapy as an option. Also the result was revision of the cells to a different cell phenotype -- which could case serious side effects. Lots of questions still to be answered. Very interesting, but lots of questions.

Re:Cancer vs common cold

[ledow]

I should hope we do.

Pissing about curing someone's sniffle that'll be gone tomorrow when we could have spent that time/money pushing cancer research - no matter how slow and small a contribution - seems a bloody bad trade-off.

Re:Cancer vs common cold

[Kohath]

The cure for a cold is to wait 2 weeks.

Re:Cancer vs common cold

[vossman77]

Who knows we may use the common cold to actually cure cancer.

Re:Cancer vs common cold

[Anonymous Coward]

(or not have sex, since... well, you know... they're probably sneezing & have a runny nose at that point, and probably shouldn't be having sex with anybody for a day or two *anyway* as a common courtesy to avoid spreading their cold to others.

The problem with hormonal birth control is that if it fails at the wrong time (ie. when the woman's egg is released), then it's basically failed for the entire cycle. Because there's no easily verifiable way for a woman to check if she's ovulated, birth control failing for a couple of days = need to use condoms for the entire cycle.

Re:Cancer vs common cold

[Archangel Michael]

I saw a movie like this once ... it had zombies or something.

Re:Cancer vs common cold

[Anonymous Coward]

Which is really not a bad trade-off, and many things cause interruption to a cycle (missed pills, whatever). Anyone in a long-term on-pill relationship will have dealt with months of "cautious time".

So you make that decision at game-time - is your cold worth bearing out or not ? Stupid to not allow people to make this decision for themselves if it's really a cold-curing pill.

Re:Cancer vs common cold

[TimSSG]

I saw a movie like this once ... it had zombies or something.

I am ready a book series about a Flu vaccine that triggered Zombie outbreaks across the USA. Tim S.

Re:Cancer vs common cold

[eis2718bob]

Fighting cancer is fighting evolution itself.

Your body is composed of some 40 trillion cells. Each one comes from a line of cells going back billions of generations, every one of which succeeded in reproducing and projecting itself into the future. DNA is not easily squelched.

Re:Cancer vs common cold

[MobileTatsu-NJG]

Yes, but they also have certain commonalities. Just like almost all gas engines have a fuel pump, if you want to kill a gas engine, you might want to consider cutting power to the fuel pump. They have have different types of ignition systems, they might have forced air induction, they might be 4, 6, 8 cylinders, etc... but most cancer cells do share a lot of common pathways.

That's a good point. Mind if I forward your post to my doctor?

Re:Cancer vs common cold

[Anonymous Coward]

It's not outrageous without a lot more background information than what you've stated. Hormonal side effects like that are significant enough to warrant further study before approval. Maybe the pharma company wasn't willing to sink more money into it? Maybe the pharma company did sink more money into it and discovered something worse than birth control failure that would prevent them from even trying to go back to the FDA? Bottom line, stop looking for reasons to be outraged in the rumor mill you fucking git.

Re:Cancer vs common cold

[blue9steel]

Fighting cancer is fighting evolution itself.

Good, Americans like a war we can really sink our teeth into.

Re:Cancer vs common cold

[reverseengineer]

E47-inducible cell lines were generated by infection with
a retroviral vector expressing E47 fused to a tamoxifen-inducible
modified estrogen receptor (MER).

The way this was done was really clever: it uses a virus that causes cancer to treat cancer. Specifically, the retroviral vector is an engineered strain of Moloney Murine Leukemia Virus (MoMuLV), which can cause leukemia in mice (it is not known to cause disease in humans, though retroviral infection does carry at least a small risk of mutagenesis). The viral vector inserts a gene that expresses the protein E47, which acts in a variety of ways to make cancer cells revert to acting like healthy cells.

This is an exciting idea, though as the press release notes, "we are screening for molecules—potential drugs—that can induce overexpression of E47." That's a way of noting that retroviral vector gene therapy is in its infancy, and that it would be much better if we could find a small molecule instead.

These findings prompted us to ask whether
the growth arrest and acinar gene expression induced in vitro
might be sufficient to diminish the tumor-forming potential of
these aggressively growing cells. Indeed, temporary induction of
E47 for 2 to 8 days in vitro produced stable cell cycle arrest and
trypsinogen expression in transplanted human PDA cells. It will
now be of interest to investigate the effects of E47 on the growth
dynamics of established tumors.

And also the above- established tumors notoriously mutate and become genetically heterogeneous over time, greatly increasing the chances that at least some of the cancer cells are resistant to whatever line of attack you throw at them. Cancer cells that have mutant forms of E47's targets wouldn't be reprogrammed. Still, any advance against pancreatic cancer is highly welcome.

Re:Cancer vs common cold

[Stolpskott]

I bet we find a cure for all kinds of cancers before we find a cure for the common cold.

I would be willing to bet that the big pharma companies will never actually produce a cure for cancer. Treatments, for sure, but not a cure.
The reason being economics - let's say that a person with cancer was willing to hand over every last dollar they own for a cancer cure. Big Pharma would make a reasonably large sum of money off that person, but it is a one-off sale. So to get more money, they need to get it from another poor sod with cancer. Now consider that there is not a cure, but a "treatment" for cancer that must be taken every day for the rest of your life. Big Pharma cannot make anywhere near as much per tablet for that, but it is an on-going source of income over the course of 5, 10, 20 years, and will almost certainly result in more money for the company.

Re:Cancer vs common cold

[Zordak]

I'm reading a book about a Zombie outbreak that triggered a flu pandemic across the USA. But it's a really bad flu strain, with like a 17% higher mortality rate than Swine Flu.

Re:Cancer vs common cold

[Anonymous Coward]

The commonality amongst cancers is that they are aneuploid. This has been known for quite some time but is ignored in studies like this. The cells will not be "normal" after this treatment unless it somehow corrected the aneuploidy (this was not measured, but there is no reason to think it did). Since both point mutation rate and chromosomal instability are increased in most aneuploid cells they easily adapt to treatments targeting specific proteins/DNA sequences over time, leading to drug resistance. This study only observed mice for 5 weeks which is not very long. It may not have been long enough for the cells to adapt. Also, the tumorigenic cells were already expressing the "growth-suppressive" protein when transplanted into mice, the treatment was not applied in vivo.

Even if some way of activating this protein or mimicking it's effects in vivo can be devised, it is unlikely be translated into a cure until there is a method allowing sustained targeting of aneuploid cells. If we had such a method, we would want to get rid of the cells rather than only suppress their growth since a subset is likely to become resistant to any treatment we can apply eventually.

That isn't to say the information reported by Kim et al. is not useful (assuming it is accurate). Rather my point is that the hyping of scientific findings really needs to stop. It is out of control and leading to the spread and sustenance of misinformation. In the researcher's favor, I do note they only talk about "combating" the disease rather than curing it.

Re:Cancer vs common cold

[fatwilbur]

There's a really good documentary on the evolution of cancer treatments on PBS right now, and one stark fact (that I've noticed elsewhere prior as well) made obvious is just how generic the term cancer is. It's really just any of a million specific types of genetic errors that lead to uncontrolled growth.

Even within the same type of tissue, you can have multiple types of mutations that result in the same effect (uncontrolled growth), hence the different "types" of pancreatic cancer for example. The concept of a "cure" has been reduced down to finding compounds, antibodies, organisms, whatever that can identify and trigger some change only in those cells with that specific genetic mutation. Some of them have external markers and make it a bit easier..

This was the one thing that gives me hope about eventually curing cancers en masse, is that they are essential dumb.. they do not evolve like the common cold, it is a specific mutation that one we find a way to reverse, will have cured it forever.

It was quite amazing watching in the last episode, a woman who had left hospital with a death sentence in stage 4 breast cancer, to be called into a stage 1 herceptin trial and be 100% cured and alive twenty years later. This drug was simply based on antibodies which could recognize the specific markers left by her specific mutation, and 100% cured with no side effects.. We, as humanity, can and will find a way.

Re:Cancer vs common cold

[Xyrus]

Yes, but they also have certain commonalities. Just like almost all gas engines have a fuel pump, if you want to kill a gas engine, you might want to consider cutting power to the fuel pump. They have have different types of ignition systems, they might have forced air induction, they might be 4, 6, 8 cylinders, etc... but most cancer cells do share a lot of common pathways.

The problem isn't that they share certain characteristics. The problem is that they share the same characteristics with healthy cells.

Killing cancer cells is easy. Killing cancer cells without also destroying everything else is a very hard problem to solve. If this protein can force cancer cells back into healthy cells (or at least self-destruct) WITHOUT negatively affecting healthy tissues then this would be significant.

Re:Cancer vs common cold

[Anonymous Coward]

Was the 'fucking git' part really necessary?

Re:Cancer vs common cold

[storkus]

Killing cancer cells is easy. Killing cancer cells without also destroying everything else is a very hard problem to solve. If this protein can force cancer cells back into healthy cells (or at least self-destruct) WITHOUT negatively affecting healthy tissues then this would be significant.

Exactly! This is precisely why this is not a small step, and hopefully will lead to similar research and treatments on other cancers.

Another way to put the significance of this is a magic chemical or drug that turns zombies back into normal people. (Ok, cancer is the opposite of a zombie, but you get the point.)

Re:Cancer vs common cold

[Anonymous Coward]

"just how generic the term cancer is. It's really just any of a million specific types of genetic errors that lead to uncontrolled growth."

This is just misinformation: "In contrast to normal cells, aneuploidy--alterations in the number of chromosomes--is consistently observed in virtually all cancers." (https://www.ncbi.nlm.nih.gov/pubmed/15549096)

This was the one thing that gives me hope about eventually curing cancers en masse, is that they are essential dumb.. they do not evolve like the common cold

Then there would be no drug resistance that develops. More misinformation.

It was quite amazing watching in the last episode, a woman who had left hospital with a death sentence in stage 4 breast cancer, to be called into a stage 1 herceptin trial and be 100% cured and alive twenty years later.

That does not sound representative according the info here: "If 1000 women were given standard therapy alone (with no trastuzumab) then about 900 would survive.. If 1000 women were treated with standard chemotherapy and trastuzumab for one year, about 933 would survive (33 more women will have their lives prolonged), about 740 would be free of disease recurrence (95 more women will not experience the disease return)" (https://www.ncbi.nlm.nih.gov/pubmed/22513938). Your anecdote suggests that it is much more effective.

If you gathered this information from a documentary, I am sorry but it is a highly misleading one.

Re:Cancer vs common cold

[Anonymous Coward]

There's a really good documentary on the evolution of cancer treatments on PBS right now...

I agree it's a good series. I also recommend the book it is based on - The Emperor of all Maladies by Siddhartha Mukherjee.

Re:Cancer vs common cold

[Anonymous Coward]

We, as humanity, can and will find a way.

I do agree with this sentiment, even that a cure/prevention may be much simpler than expected. Unfortunately, I suspect it will require dropping the focus on point mutations while requiring independent replications and more careful interpretation of the various evidences that have built up over the decades.

This might make a lot of people feel bad/embarrassed/angry. To choose the most sacred cow I can think of, say hypothetically that curing/preventing cancer will require the realization that smoking does not cause cancer and never did. A lot has been done and said based on that premise. I'm not saying that specifically is the case, the thought experiment just allows us to imagine how certain ideas can become obstacles to progress.

Re:Cancer vs common cold

[stevedog]

Actually, I've never really thought about it, but cancer is not that different from a zombie. It is a cell that should have died (self-destruction by apoptosis or recognized as abnormal by nearby phagocytes), but didn't, and precisely because of what should've gotten it killed, is now behaving abnormally and often in a way where it is trying to replace the remaining normal entities with more of itself.

Re:Cancer vs common cold

[Anonymous Coward]

Peter Duesberg, Daniele Mandrioli, Amanda McCormack and Joshua M. Nicholson. Is carcinogenesis a form of speciation? Cell Cycle 10:13, 2100-2114; July 1, 2011. http://www.davidrasnick.com/Cancer_files/Duesberg%202011%20speciation.pdf

Re:Cancer vs common cold

[Anonymous Coward]

The premise of Mira Grant's Feed is that zombies were created by two experimental viruses being combined/released by ecoterrorists, one of which cured the common cold and the other cured cancer. The result being a post-apolcolyptic world where there are zombies but no colds or cancer.

Re: Cancer vs common cold

[Anonymous Coward]

Err, some Americans are already proudly fighting the good fight against Evolution. Even the four father's were against it. Didn't you know?

Re:Cancer vs common cold

[muecksteiner]

Close, but no cigar. Big Pharma actually has a very good reason to sell you a cure for cancer (as opposed to a chronic disease treatment): namely, that once cured, you go on living as a once again healthy human being. So you can once again be fully functional, earn money, and hopefully grow a lot older than you would have with chronic cancer.

By itself, this increased wellbeing of yours is of course of no concern to the bean counters in said companies. But chances are high that you'll eventually develop some *other* sort of cancer, sooner or later. Or some other $complicated_disease, for which you will need the services of Big Pharma.

The difference is really between slowly killing your customers with a not 100% efficient "cure", or actually curing them - so they can become repeat customers at some later point in time. Which makes the whole thing a no brainer, really: *especially* from an accounting viewpoint.

Re:Cancer vs common cold

[Stolpskott]

Big Pharma actually has a very good reason to sell you a cure for cancer (as opposed to a chronic disease treatment): namely, that once cured, you go on living as a once again healthy human being. So you can once again be fully functional, earn money, and hopefully grow a lot older than you would have with chronic cancer.

Once cured of your cancer though, you are no longer a revenue stream for the company. Unless you count the potential for revenue from other illnesses you might contract, but for the typical bean counter a potential revenue stream like that, which would probably be shared with other Big Pharma companies, so do little or nothing for "this" company's bottom line.
As for the whole bean counter argument, that is exactly who runs pretty much all of the Big Pharma companies - accountants and MBAs whose only concern is how to maximize profits. Admittedly I have no citation for that, other than a trawl through the Bloomberg and Reuters data on Pharmaceutical companies to see who are on the Boards of Directors and what their qualifications are. But a brief review of the Boards for Johnson & Johnson, Pfizer, Roche, GlaxoSmithkline, Novartis, Sanofi, AstraZeneca, Abbot, Merck, and Beyer, all show basically the same make-up - lots of "business" people, and a vanishingly small technical/medical representation.

Re:Cancer vs common cold

[Anonymous Coward]

Aneuploidy can be very different between different cell types too. It's also hard to target.

True

[goldcd]

But my memory of what's special about Pancreatic Cancer - is that you are f*cked to a high degree of certainty if you get it.

Not the most common type of cancer, and there are many types of it - but for those with this cancer, in this place, it's pretty damn important as there weren't a surfeit of alternatives.

Re:True

[alvinrod]

While I doubt that's the exact medical terminology used, it's quite correct.

The five year survival rate is only 6% although it apparently can get up to ~20% in limited circumstances.

If this works as well hoped, it would be a rather big deal because right now it's practically a death sentence.

Re:True

[fahrbot-bot]

While I doubt that's the exact medical terminology used, it's quite correct. The five year survival rate is only 6% although it apparently can get up to ~20% in limited circumstances. If this works as well hoped, it would be a rather big deal because right now it's practically a death sentence.

Although, for some perspective, from Wikipedia for Glioblastoma multiforme (brain tumor):

GBM is a rare disease, with an incidence of 2–3 cases per 100,000 person life-years in Europe and North America ... Median survival with standard-of-care radiation and chemotherapy with temozolomide is 15 months. Median survival without treatment is 4½ months.

Sure, it's *way* more rare, but treatment options suck. My wife Sue died of this in early 2006, just 7 weeks after diagnosis - her only complaint was a persistent headache and mild disorientation. Remember Sue...

Re:True

[Burdell]

Yep. My grandfather was an outlier - he lived IIRC about 8 years, and about 7 of that pretty good outside of chemo IIRC every 6 weeks. A former cow-orker was diagnosed and didn't make 6 months.

From what I understand, part of the problem with the common forms of pancreatic cancer is there aren't many symptoms until it spreads, and once it spreads, it is aggressive and kills rapidly.

Re:True

[Anonymous Coward]

Sorry for your loss. The memorial website is nice.

But sadly,

[roc97007]

too late for Randy Pausch.

Sounds like a reverse mad cow diease type deal

[omfglearntoplay]

I'm sure that oversimplifying it a million times over, but it sounds cool at a reading the headlines level.

Difficult cancer

[Etherwalk]

But Pancreatic cancer is, on the whole, really uncool.

It's harder to operate on than most cancers and has a higher kill rate. Progress like this is very helpful.

Breaking News: They are all doing it wrong!

[John Bokma]

cuz the arm chair expert just said so!

Sad

[Anonymous Coward]

I should be happy any time something is found to help fight a disease like this. But.. selfish as it may be.. having already lost my grandfather to this one reading that maybe he could have been helped a few years later makes me feel sad.

Inverse!

[Anonymous Coward]

Introducing an Inverse-Protine to convert a "healthy cell" into a Pancreatic Cancer Cell.

Ah. A weapon! We use it and introduce it to the Country water supply and distribution system. Set Stop Watch, "Click". Sit back and wait.

Thank you. I have what I need to know.

Just to make it clear a cure for the common cold

[NotSoHeavyD3]

Would have to have all of the following attributes.

It would have to act very quickly since for most people if you do nothing it's over in 7 days.

It would have to be very safe because for most people if you do nothing it's over in 7 days.

It would have to be very cheap because for most people if you do nothing it's over in 7 days.

Re:Just to make it clear a cure for the common col

[Anonymous Coward]

Nope, common cold can cause brain swelling in children:
http://www.dailymail.co.uk/news/article-1324793/Danielle-Brooker-dies-common-cold-virus-causes-fatal-brain-infection.html

No matter how rare or unreliable (aspirin also supposedly does that, it is caused Reye's syndrome) that claim is we will all need to get vaccinated once it has been declared effective. I don't mean to be insensitive to the rare person who actually may actually suffer due to getting the cold or those who have been helped with other problems where public health measures have been effective, but that is really all it will take.

Nobel? Where's Mr. Nobel when you need him?

[Anonymous Coward]

This is not just praiseworty, this is prizeworthy.

Nature?

[louic]

Assuming this result is real, why is it not published in Nature? (I do not mean to criticise, I am genuinely curious)

Re:Nature?

[Anonymous Coward]

So, given my big background in biochemistry, I can say that the reason this is not Nature material is probably b/c it is a pancreatic cancer cell line, not anywhere near a clinical trial. Furthermore, I derive from the abstract that they altered the cell line by engineering expression of the protein in the cells. This is really something you could not do very straightforwardly at all in the human body.

Re: Nature?

[Anonymous Coward]

Did they start letting people describe their methods yet? Around the turn of the century it got unbearable. It was slightly, but not much, better last I tried to actually figure out what someone did.