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Pancreatic Cancer's Achilles' Heel
ScienceNOW Daily News ^ | 21 May 2009 | Stephanie Pappas

Posted on 05/23/2009 10:05:08 PM PDT by neverdem

Enlarge ImagePicture of tumor

Blocked. Chemo drugs (green) can't penetrate a pancreatic tumor (blue). White stroma (insert) separates blood flow from tumor cells (light brown).

Credit: Stefanie Reichelt, Michal Al Jacobetz, and Kenneth P. Olive; (inset) Kenneth P. Olive

Almost 95% of pancreatic cancer patients die within 5 years of diagnosis, and traditional chemotherapy does little to save their lives. Now, cancer researchers think they know why--and how they might get around the tumor's defenses. The work "has huge ramifications for how we approach therapy of this disease," says Margaret Tempero, an oncologist at the University of California, San Francisco.

Cancers almost always grow in the duct system of the pancreas, a spongy handful of tissue nestled against the stomach that produces digestive enzymes and hormones such as insulin. Although these tumors are deadly when they spread to other parts of the body, malignant cells are surprisingly sparse in the pancreas. Biopsies typically turn up a few scattered cancer cells amid masses of stroma, webs of tough, fibrous connective tissue that look like a "big piece of gristle," says oncologist David Tuveson of the Cambridge Research Institute in the United Kingdom.

That gristle, Tuveson and his colleagues found, shields pancreatic tumors from blood-transported treatments like chemotherapy. Using mice genetically engineered to develop pancreatic cancer, the team mapped the blood supply of tumors using chemical tracers to mark blood flow. They found very few blood vessels and just a third as much circulation as in normal tissue. Human pancreatic cancer samples told a similar story: lots of fibrous tissue, few blood vessels.

If his team could shrink the stroma, Tuveson wondered, could doctors target the cancer cells hiding inside? The group focused on the whimsically named hedgehog signaling pathway, which helps organize the structure of organisms during embryonic development and promotes the growth of stroma. The researchers treated mice with IPI-926, a drug that suppresses the hedgehog pathway. Other mice got a common chemotherapy drug, whereas yet another group got IPI-926 and the chemo drug.

As the researchers had hoped, IPI-926 dramatically shrank the stroma. And there was a bonus: The drug also increased the number of blood vessels inside the tumors by threefold to fourfold. Feeding a tumor with extra blood might normally promote cancer growth, but in the case of pancreatic cancer, it was good for drug delivery; mice given a combination of chemo and IPI-926 nearly doubled their survival, from a median of 11 days to 25 days, the researchers report online today in Science. It's not a cure, Tuveson cautions, but the results leave him optimistic. "If we were to double the survival of pancreas cancer patients that had advanced disease, instead of dying in 6 months, they'd die in 12 months," he says. Compared with previous medical interventions, "that would be a bigger impact than we've ever seen."

Although other factors besides blood flow might affect chemotherapy resistance, the study "demonstrates pretty nicely that the cancer cell is not the only thing we need to be worried about," says oncologist James Abbruzzese of the M. D. Anderson Cancer Center in Houston, Texas. "We really should be paying more attention to these cancer-stroma interactions." The next step, he and Tempero say, is to find out if IPI-926 has any potential as a drug for humans and if it is safe to use on tumors outside the pancreas.


TOPICS: Culture/Society; News/Current Events; Testing
KEYWORDS: cancer; hedgehog; hedgehogsignaling; pancreaticcancer
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1 posted on 05/23/2009 10:05:09 PM PDT by neverdem
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Bookmark


2 posted on 05/23/2009 10:11:07 PM PDT by potlatch
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To: neverdem

Looks promising.

It would be so great if they could find a cure to this terrible disease. It boggles the mind that so much effort is spent researching AIDS and other STDs, which already have a cure through behavioral prevention(for the most part), while there is a deadly disease like Cancer that can strike anyone at any time.


3 posted on 05/23/2009 10:16:34 PM PDT by KoRn (Department of Homeland Security, Certified - "Right Wing Extremist")
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To: KoRn

Amen to you. 50 years ago my Mom died at 40 from pancreatic cancer. She lived for four painful months after diagnosis. Here, 50 years later, the prognosis for a 40 year old with the disease would be little better than hers. Your point about Aids is one I’ve thought about. Perhaps there was something in my mom’s lifestyle that brought on the disease. But we do not know. We do know how HIV is transmitted and how it can be prevented. The gay community’s determination to have unfettered sex is the driving force behind the spending on HIV to the detriment of diseases like pancreatic cancer.


4 posted on 05/23/2009 10:41:41 PM PDT by xkaydet65
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To: neverdem

I don’t mean to be a pessamist, but, will cancer ever really be cured? There’s too much money to be made with chemotherapy and “cancer research”.


5 posted on 05/23/2009 11:00:05 PM PDT by diamond6 (Is SIDS preventable? www.Stopsidsnow.com)
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To: neverdem

bttt.


6 posted on 05/23/2009 11:02:03 PM PDT by rdl6989
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To: diamond6

Yes, I believe cancer can be cured someday. With the help of the human genom project (and it’s sister projects: human disease/cancer genom research) scientists are slowly learning what makes cancer tick at the genetic/molecular level. This will result in new drug therapies, new drug delivery techniques, and finding “weak spots” in cancer cells.

At first, the goal might be to simply “stalemate” the cancer turning into a chronic disease. After that, training the immune cells to do the dirty work (or finding ways to outright kill the cancer via starvation or tricking the cancer cells to “self-distruct”).

The holy grail will be to find the gentic defects ahead of time and repair them or to make cancer vaccines.

It wasn’t too long ago when most cancers were simply fatal and nothing much could been done (if anything). After the 1950’s, with radiation and chemo, it was a “sledgehammer” effect often doing more damange than good (a crap shoot on what killed you first, the radiation of the cancer). Now, it’s starting to get a little more refined.

Yes, we are making progress (I’m living proof of it, I’ve been cured of my cancer and have been free of the disease for over 18 years).


7 posted on 05/23/2009 11:14:53 PM PDT by ak267
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To: neverdem

I hope this is the key, though it’s a couple of years too late for my dad.


8 posted on 05/24/2009 1:09:18 AM PDT by Tex Pete (Obama for Change: from our pockets, our piggy banks, and our couch cushions!)
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To: xkaydet65

I hope they are able to save Patrick Swayze. He’s going steadily downhill.


9 posted on 05/24/2009 1:20:43 AM PDT by libh8er
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To: diamond6
will cancer ever really be cured?

given the complexity of the human body I for one doubt cancer will ever be "cured" it appears at this stage in medical history that stopping the body from turning on itself or abnormal cell growth/regeneration especially with advanced age is a pretty tall order but I do think we can make a lot of progress, especially with cancers that are slow to metastasize and more prone to affect younger otherwise more healthy folks some sort of abnormal cell growth after aged 75 or so is nearly universal...just depends on if it's the ominous sort

i agree that we waste money on preventable disease research for political reasons.. which is why prostate cancer gets less funding than breast cancer too btw...and less exposure even though by certain ages prostate cancer is just about a given for over 80 year old men....while breast cancer for women is not, yet women's groups and homosexual groups will tell you no one pays attention to their diseases.. btw...don't let PSAs scare you, it's the velocity of PSA changes that matter more and yes....prostate exams and that damn smear reflex hurts like hell...i will never understand homosexuals fascination with all that

10 posted on 05/24/2009 1:32:24 AM PDT by wardaddy
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To: KoRn

Part of that is because while AIDS has a few variants and other STDs are specific and relatively simple, there is no “cancer” disease. Cancer is a bewildering array of diseases with causes and contributions we only begin to understand on a cancer-family-by-family basis. Cancers evolve in response to treatment, in response to their own evolution, in response to the body’s response. A better comparison than AIDS to “cancer” would be to take a single cancer, like acute myeloid leukemia, and understand that there are easily a dozen frequently seen “types” of that cancer, stratified by subtype, by WHO classification, by cytogenetics, and by genetic mutations.


11 posted on 05/24/2009 1:34:21 AM PDT by Sandreckoner
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To: diamond6

“I don’t mean to be a pessamist, but, will cancer ever really be cured? There’s too much money to be made with chemotherapy and “cancer research”.”

So then it’s your belief that everyone from big pharma to the research hospitals to the private consortiums to the university labs who are all spending their own money, their own profits, their own borrowed investment money, state and federal grants - they’re all not really trying, and if they find something there’s a large conspiracy to squelch it, maybe a gentleman’s agreement that anyone who actually finds something will toss it in the trash?

Try reading pubmed or any of the numerous cancer research journals. You might find yourself disabused of this astonishingly ignorant meme quickly. There’s reason to be pessimistic about a “cure” for cancer, but not because vast amounts of money and some of the most advanced technology and knowledge on the planet aren’t working on cancers around the globe.


12 posted on 05/24/2009 1:37:17 AM PDT by Sandreckoner
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To: neverdem

Pancreatic cancer is one of the worst. The mother of one of my good friends had it. This was a lady who took impeccable care of herself, played competitive tennis into her sixties, and looked easily 15 years younger than her actual age. She lasted less than a year. This would be great news if it pans out.


13 posted on 05/24/2009 1:50:12 AM PDT by balch3
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To: Sandreckoner

Please Lord, help these people find a cure for this nasty disease. I lost my young 70yo mother to this cancer a year and a half ago. Less than 2 months after diagnoses.
Even her primary care dr told her that her choice of No treatment was right, as his med school friend, a pancreatic cancer surgeon that came down with it chose no treatment as even he knew it didn’t work and only bought you a little time,(much of it suffering effects of chemo/radiation).
Of course her Dr knew her well and knew once she made up her mind, she wouldn’t change it. My brother was livid he told her that, but it helped my mom know she was making the right choice. I supported her choice along with my sister, but Oh how we miss her.


14 posted on 05/24/2009 1:54:15 AM PDT by MarineMom613 (Remember 9/11 ~ www.the912project.com)
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To: wardaddy

I’ve always thought that the medical profession would get a lot more cooperation with testing and screening if they’d put more effort into coming up with tests that are less painful and leave the patient with their dignity intact. Your prostate example is a good one. Another is, whay after 500+ years, haven’t they come up with a better way of delivering medication than through a hypodermic needle? I know there are patches and such, but it’s still the primary method, and it’s barbaric.


15 posted on 05/24/2009 1:55:16 AM PDT by balch3
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To: balch3

btw...having cared for several family members dying of what used to be called old age but was really cancer (an unremarkable disease in folks over 70)...

I will not take chemo unless the odds are good of full recovery or at least 5 years median survival minimum

chemo is barbaric and ruins those last precious months


16 posted on 05/24/2009 2:08:06 AM PDT by wardaddy
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To: balch3

ditto radiation...only slightly less brutal


17 posted on 05/24/2009 2:08:37 AM PDT by wardaddy
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To: neverdem
I have this bubble on my back right hip, that if I squish really hard,
eliminates my back pain. But after a while (1-day) it comes back.

I have no idea what it is, but it gives my right back hip spasms.
And yes, it hurts badly.


It's ok if you say I'm a dead man walking.

18 posted on 05/24/2009 2:15:24 AM PDT by MaxMax (America's population is 304-Million. Obama must punish America for the other 4.7 Billion)
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To: neverdem
"If we were to double the survival of pancreas cancer patients that had advanced disease, instead of dying in 6 months, they'd die in 12 months," he says. Compared with previous medical interventions, "that would be a bigger impact than we've ever seen.""

This kind of "success" claim is bogus. The rats still die of the disease. They are NOT cured. When 60% of the rats DON'T die of the cancer, THEN one can claim success. Cancer "researchers" have done this from day one of cancer research, drugs or techniques that extend life by 10% are touted as "great breakthroughs".

19 posted on 05/24/2009 3:07:58 AM PDT by Wonder Warthog ( The Hog of Steel)
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To: Sandreckoner
So then it’s your belief that everyone from big pharma to the research hospitals to the private consortiums to the university labs who are all spending their own money, their own profits, their own borrowed investment money, state and federal grants - they’re all not really trying, and if they find something there’s a large conspiracy to squelch it, maybe a gentleman’s agreement that anyone who actually finds something will toss it in the trash?

Try reading pubmed or any of the numerous cancer research journals. You might find yourself disabused of this astonishingly ignorant meme quickly. There’s reason to be pessimistic about a “cure” for cancer, but not because vast amounts of money and some of the most advanced technology and knowledge on the planet aren’t working on cancers around the globe.

Nice rant, but it doesn't address the fact of the cancer industry as a very big business (hundreds of billions per year) which would end if a cure was acknowledged. Look around at this big wide world - ever see a business that big voluntarily ended?

Or should we all just trust the halos that come with those white coats?

20 posted on 05/24/2009 3:53:23 AM PDT by Talisker (When you find a turtle on top of a fence post, you can be damn sure it didn't get there on it's own.)
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