University of Rochester discovers source of cancer immunity

[Vekseid]

http://www.rochester.edu/news/show.php?id=3479

Despite a 30-year lifespan that gives ample time for cells to grow cancerous, a small rodent species called a naked mole rat has never been found with tumors of any kind—and now biologists at the University of Rochester think they know why.

The findings, presented in today's issue of The Proceedings of the National Academy of Sciences, show that the mole rat's cells express a gene called p16 that makes the cells "claustrophobic," stopping the cells' proliferation when too many of them crowd together, cutting off runaway growth before it can start. The effect of p16 is so pronounced that when researchers mutated the cells to induce a tumor, the cells' growth barely changed, whereas regular mouse cells became fully cancerous.

"We think we've found the reason these mole rats don't get cancer, and it's a bit of a surprise," says Vera Gorbunova, associate professor of biology at the University of Rochester and lead investigator on the discovery. "It's very early to speculate about the implications, but if the effect of p16 can be simulated in humans we might have a way to halt cancer before it starts."

...

This sounds potentially quite awesome, especially if it can be tailored to the specific growth and regenerative needs of humans.

[Vekseid]

Erp. Added link.

[SleepyWei]

Score one for the ugly rodent that lives a long time. I'm very interested in how this research will go. Keeping my fingers crossed.

[Sabby]

A cure for cancer is seen as a wistful fantasy... everyone wants it, many people are seeking it, but sadly, many believe its impossible, no matter how badly they want to believe otherwise. At this point, a cancer cure is our Holy Grail.

But even saying this, I wonder how the world would react if suddenly a cure was found :)

[Kate]

bring it on...

[Nadir]

 Does anyone else wonder what the hell happened to pre-historic mole rats to make them non-cancer-able?

[Rhapsody]

I lost one grandmother to pancreatic cancer, and my grandfather just had his bowels removed to halt the early (very early) stages of colon cancer.  Keep this research going; I'm not the only one who's personally interested in this.

[Beguile's Mistress]

I've lost family and close friends to cancer.  I wish there was a cure or a way to prevent it, too. 

Here's another out of the ordinary treatment/preventative for cancer using radio waves.  I believe this story was also reported on "60 Minutes."

http://www.rd.com/living-healthy/radio-waves-and-the-search-for-a-cancer-cure/article26497.html

[Vekseid]

Does anyone else wonder what the hell happened to pre-historic mole rats to make them non-cancer-able?

Possibly evolving near high concentrations of uranium deposits, or something similar.

[DarklingAlice]

Possibly evolving near high concentrations of uranium deposits, or something similar.

I think it is probably even simpler than that. If the article is correct without this gene it is the only thing that allows the naked mole rat to live to the ~30 years that it does. The article also points out that naked mole rats show little sign of age until very late in their lives. I would guess that this means that they stay sexually active and childbearing through most of their life. So along comes this mutation and suddenly one mole rat queen is living significantly longer than all the other mole rat queens and all of her progeny will live longer, and then their progeny, and you easily outcompete your short lived brethren just by outliving  them and producing significantly more progeny.

Also, pubmed link to the abstract for anyone who is interested:
http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=search&term=mole+rat+p16

Not to be cynical, but we do need to remember that even if we do find a way to integrate it into humans we need to be aware of any potential side effects. Also note that p16 no more grants cancer immunity than pRB or p53, mole rats just have all three where we humans do not, giving them a significantly lower chance of developing cancer within their lifespan. The most it can do is provide another layer of certainty, bumping the approximate (natural) cancer risk per cell division from ~10^-18 through 10^-30 to ~10^-24 through 10^-36 (which while naked mole rats don't have a statistical chance of in their thirty years we might still see incidences of in our eighty). Still this would be an amazing boon if we can work it and the University of Rochester deserves congratulations for isolating this gene.

I would also be interested to see what happened if set up a knockout mole rat without this gene, induce a tumor, and then reinsert the gene through a viral vector or other such mechanism. Can this thing actually suppress formed tumors? Or at least stop their progression to malignancy?

[Trieste]

I will freely admit that I just read Veks' synopsis and did not click on the article; perhaps it answers this question.

However, I confess to being a little confused. There are a lot of cells with anti-crowding genetics; it's the reason your liver is not the largest organ in your body, for instance, or why your kidneys are not the size of your head. One of the basic traits of the genetic mutations that cause tumors (and cancer) is the disabling of the natural claustrophobia that cells have.

This is not news. This is taught in genetics classes across the country.

So I'm wondering why the discovery that these rats have such a common genetic trait is ... news. It's good that those genes resist the mutations more robustly than other sets of genes, but when you get right down to it, cancer is a huge series of mutations that involves the disabling of failsafes and the enabling of certain unhealthy behavior in ... a single cell. It just takes one cell.

Edit: I should probably make it clear that I'm not exactly pro-cancer or something crazy. Yay, breakthrough, etc - but I dislike being patronized and patted on the head by being shown a new version of old news.

[DarklingAlice]

However, I confess to being a little confused. There are a lot of cells with anti-crowding genetics; it's the reason your liver is not the largest organ in your body, for instance, or why your kidneys are not the size of your head. One of the basic traits of the genetic mutations that cause tumors (and cancer) is the disabling of the natural claustrophobia that cells have.

Normal cells have what is known as density dependent inhibition of growth, the loss of which is key to cancer. p16 appears to be a fallback mechanism, sort of a safety valve that rigidly enforces this property. In short it is true that all animals have a system for this, but mole rats seem to be the only animal we know about that have two systems to grant this same property. And it appears that this is a great boon for them.

So I'm wondering why the discovery that these rats have such a common genetic trait is ... news. It's good that those genes resist the mutations more robustly than other sets of genes, but when you get right down to it, cancer is a huge series of mutations that involves the disabling of failsafes and the enabling of certain unhealthy behavior in ... a single cell. It just takes one cell.

The thing is (as I understand it) that these genes don't resist mutation more robustly. There is still the standard 10^-6 chance per cell division. For instance to induce unregulated cell growth in me, you would need to disable either p53 or pRB (a 10^-6 chance per cell division). To cause unregulated growth in a mole rate you would need to disable p53 and pRB or p16 and either p53 or pRB. Any of these things being a 10^-12 chance. And that is only the start of the process of oncogenesis. You would most likely need 2 other mutations to even get a benign tumor and 4-5 to attain malignancy. Basically yes this is stilla  series of failsafes. Cancer immunity is a myth but putting so much as one more failsafe in the chain decreases the possibility of cancer exponentially.

[Trieste]

Good deal - I was sitting here going, "So they have the mighty-mouse of p16? It can still mutate, or it can be bypassed, or or or..."

'Cause, I mean, it's not like you just have to disable that, but then you have to (as one example) have rampant lack of apoptosis so that you have the overcrowding of cells and then new cells and the DNA damage and and and...

It's such a big mess.

[Nadir]

Possibly evolving near high concentrations of uranium deposits, or something similar.

I read this and thought, 'Or maybe they leave near a lot of Brazil trees!'

(Because, as everyone knows, the Brazil nut is the largest source of radioactivity of any food in the world. Just a handful will set off the alarm systems in a powerplant!)

But then my brain caught up with my tea-fed logic reminded me mole rats live in East Africa. *Siiiiiigh*