Most cases are discovered after some symptoms persist or more severe indications, such as jaundice, occur.
Some groups are looking for a better way to screen for pancreatic cancer, in hopes of catching it earlier. "There's a big push for developing a blood test," says Philip Arlen, president and CEO of Neogenix Oncology, Inc., a company that is looking into both diagnostics and treatment for pancreatic cancer. They have found a couple of genetic markers that are present in pancreatic cancer but not in normal tissue. The goal, says Arlen, who previously worked as a researcher at the National Cancer Institute, is to develop something akin to a PSA (prostate-specific antigen) test for prostate cancer.
There are clues, for example, that pancreatic cancer is not as much a sudden-onset disease as it often seems. After studying the accumulation of genetic mutations in pancreatic cancer tumors, researchers concluded that the disease takes an average of seven years to form a substantive tumor and closer to a decade to start moving to other organs, according to research published last October. Armed with that knowledge and the other finding of pre-malignant lesions, Arlen is hopeful that a non-invasive screening method will eventually be developed.
Widespread screening for more common cancers, such as breast, colon and prostate, have come under fire lately for leading to too many false positives and excessive follow-up treatment. With even rarer diseases, it is much trickier, Saltz points out, and would demand an exceedingly low false-positive rate. "Pancreatic cancer, although it's a terrifying disease, is rare," he says.
Trying new treatments
When pancreatic cancer is caught early, doctors will usually try to remove it surgically. As Saltz points out, however, the chances that it will come back in the next year or two are still relatively high. And the surgery itself is risky. The pancreas is lodged deep within the abdomen, surrounded by—and connected to—other major organs. "It's considered the magnum opus of a surgeon's repertoire," she says of partial pancreas removal, which is known as the Whipple procedure.
If the cancer has already spread, as it had in Steinman's case, the most common approach is chemotherapy, which "for regular pancreatic cancer, is not very effective," Saltz says. The mainstay is the chemo drug gemcitabine (Gemzar), which is one of the treatments Steinman received. In trials, some patients saw no benefit, but for a minority, it extended life by as long as a few years, suggesting that an essential molecular difference exists in their tumors.
Despite initial positive signs from chemo, and even when Steinman was doing better, "he felt like he was living with Damocles' sword over his neck—he never knew when it was going to come back," Schlesinger says. So he turned to what he knew: the immune system. "Ralph felt deeply that the key to a cure is getting the immune system revved up enough to fight off the tumor," Schlesinger says. "That wasn't such a simple thing to do."
Enlisting the immune system to fight off a cancer has long been a goal of researchers. The only immunotherapy currently approved for general use as cancer treatment is a drug for metastatic melanoma (ipilimumab, or Yervoy, approved in March). Saltz calls that approval good "evidence that it's an important avenue to explore" for other forms of cancer.
Scientist as test subject
When word spread that Steinman had pancreatic cancer, Schlesinger says, there was an outpouring of offers from fellow immunologists to try treatments they were working on—many having been made possible by Steinman's own discoveries about the immune system's dendritic cells. Not all the experimental drugs were meant to tackle pancreatic tumors; some were for skin or prostate cancer.
In all, Steinman tried eight different experimental therapies, Schlesinger says. But they were not under-the-table, backroom needle jabs, she is quick to point out. Each drug was already being tested on other patients in phase I clinical trails, and Schlesinger and Steinman went through great pains—and many hours—to ensure all of the proper institutional and government approvals were granted before he got the therapies.
The first treatment he got was a vaccine called GVAX, under development to treat prostate cancer. He also received a novel therapy that worked on a developmental pathway (the hedgehog signaling pathway) and two that were based on dendritic cells: one in which dendritic cells were created from his own blood cells that were then "pulsed with RNA that had been isolated from his tumor," Schlesinger explains; and another in which the dendritic cells were filled with "peptides that were from his own tumor." The hope was that the RNA and proteins from his tumor would help his dendritic cells stimulate his immune system to attack the cancer.
Arlen's group is testing, in a phase I trial, a monoclonal antibody to treat patients with the more common form of pancreatic cancer. Preliminary data show that the antibody finds its target with some 50 to 60 percent of patients with adenocarcinoma, he says. But that does not mean that it will leave them disease-free. And he hopes that a combination of the new approaches and the more standard drugs will yield even better results—a trial that they plan to start next year.
"I think it's far too early to say they have a treatment for any of these diseases," Saltz concludes.
Treating Jobs's cancer
Endocrine cancer, the variety Jobs had, is treated with a different variety of chemotherapy drugs. Two new drugs for this type were just approved by the U.S. Food and Drug Administration (FDA) earlier this year. Everolimus (sold as Afinitor) works by blocking the mTOR kinase target to alter cellular signaling and was approved in May. Sunitinib (sold as Sutent) blocks a vascular endothelial growth factor. "Neither is a cure—neither is a wonder drug for the disease," Saltz says. "Each provides some modest benefit. "
One form of treatment that is not recommended for most pancreatic cancer is a liver transplant. Media observers surmised that the transplant Jobs received in 2009 had been necessary because the cancer had spread to his liver. And although liver failure is a common cause of death for pancreatic cancer patients, because the liver is close to the pancreas and often gets invaded by the spreading cancer, getting a new one "is not an accepted standard form of treatment," he says, citing a lack of evidence to show that it works.
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20 Comments
Add CommentSteve jobs is a lucky guy to have survived for such a long time since he was diagnosed back in 2003.
Reply | Report Abuse | Link to thisI realize that the focus of this article is the difference between two types of pancreatic cancer, but I find it simply amazing that there is no mention of the fact that Steve Jobs' pancreatic cancer was diagnosed early and perhaps early enough that he could have had successful treatment for it (http://articles.sfgate.com/2004-08-03/business/17441322_1_neuroendocrine-tumors-survival-rates-islet). I also find it amazing that there is no mention of the fact that Jobs tried "alternative medicine" for 9 months before being treated with real medicine (http://tech.fortune.cnn.com/2008/06/13/steve-jobs-life-after-the-whipple/). I think that this article could have had a greater impact on the medical education of its readers if there was some mention of the difference between genuine medicine and so called "alternative medicine." Steve Jobs should have lived for a much longer time than he did, but the devastating tragedy is that being skeptical of conventional medicine, he decided to think different.
Reply | Report Abuse | Link to thisStrubie makes and excellent point. Jobs tried a "naturopath diet" as part of his non-science alternative "treatment". There's no way to know how long Jobs may have lived if he hadn't delayed real treatment by nine months, but it's sad that a man with such a critical mind was so credulous when it came to this life and death decision.
Reply | Report Abuse | Link to thisOf course this is a circumstantial case pieced together from news reports. Jobs had no symptoms. Insulinomas have symptoms when they are big enough to cause them -- its hypoglycemia, a condition diabetics often experience. Jobs got a "routine" abdominal scan or maybe a full body scan which was popular at the time or whatever it is billionaires do to try to "catch cancer early" and live forever. Who knows? If he had not had the scan, maybe the insulinoma becomes big enough to cause hypoglycemia in his lifetime or maybe it doesn't (its found more often in autopsies than clinically -- (as high as 10%)). IF it wasn't just "routine" and he went for a scan WITH SYMPTOMS -- the situation changes. Any half way decent doctor can put two and two together and tell you you have an insulinoma (NO BIOPSY REQUIRED) and he can send you right to the OR to get cured. When they find something on Jobs scan -- since he had no symptoms and his blood work must have been normal -- not even a hint of low glucose -- they assume he has the more common dangerous form. He himself says he thought he had only months to live. So then they tell him they need to do a BIOPSY to be sure because there are other things it may be although the chances of that were slim. Afterwards he says he cried after the doctors told him it was the very rare but very "curable" form. He didn't even rush into any surgery -- they probably told him it was benign, like 90% of them are. But meanwhile the BIOPSY was doing its dirty work -- inflaming the tumor or already seeding metastasis. By the time he had surgery it may have been too late. BIOPSY induced micrometastasis had already begun or possibly surgery on an inflamed insulinoma is more dangerous than one that isn't. Circumstantial for sure but no doubt men have been sent to jail on lesser circumstantial evidence. With full access to his medical records I think someone would have little trouble getting an involuntary manslaughter conviction in the death of Steve Jobs. Jobs was forced "all in" by those "routine scan" results. -- after that he had no real choice but to keep playing and hope to catch that hole card and get out of the game alive. Instead a "routine" scan began a long medical cascade that ended tragically yesterday. Apparently sometimes you can catch cancer too early. Obama's comments on his passing notwithstanding, I think its more horribly ironic as well as pathetically sad that one of the greatest visionaries of modern technology was himself probably done in by modern technology.
Reply | Report Abuse | Link to thisStone me Mate,
Reply | Report Abuse | Link to thisIt's a wonder I am still alive,as I had a Liver Biopsy 49 years ago when I had Hepatitis .
The Biopsy was apparently , to check on whether I had developed Diabetes .
I like the article and the points made about other key areas of Jobs' battle with cancer, but the typos and inconsistant use of contractions are bothersome. OSD--sorry. It gives me hope for shooting off quick articles for reputable media one day though (I'm awful at proofreading--ADHD too).
Reply | Report Abuse | Link to thisA common cause of pancreatic cancer is Hereditary Hemochromatosis, or HHC. No idea of his mother's ancestry, but his father's Middle East origins would make 'The Celtic Curse' an unlikely cause.
Reply | Report Abuse | Link to thisFor the most common adenocarcinoma pancreatic cancer the best first line anticancer treatment, is no more Gemcitabine (Gemzar), but the regimen FOLFIRINOX, for patients with good clinical condition.
Reply | Report Abuse | Link to thisOne statement you may have got wrong. Steve Jobs says in his 2005 Stanford address that it was the doctor who cried -- Jobs was under at the time.
Reply | Report Abuse | Link to thisYour comment was interesting and detailed, but I'm afraid I cannot evaluate it. What is your knowledge and expertise in this area?
Since the pancreatic cancer had spread to the liver, I wonder why they just transplanted a new liver. The main problem was the pancreas. Why didn't they transplant both a pancreas and a liver?
Reply | Report Abuse | Link to thisI agree that doctors reduced his lifespan. Dr. Mercola claims he chose the wrong doctor. When wealthy patients are killed , doctors are looked at as heroes and receive big payoffs. The doctors should be paid only for success.
Reply | Report Abuse | Link to thisI tried to contact Steve Jobs by mails and emails (by others, since I don't have his email). My message to him was to have him contact Weimar Institute (www.weimar.org) for his treatment. I tried partly because I knew it would be hard for his cancer to be treated by conventional modern medicine. If he listen to his body in a holistic way, his body may find a way to cure itself. Weimar Institute apply NEWSTART, a lifestyle changing regimen, developed by Seventh Day Adventists.
Reply | Report Abuse | Link to thisWhile I was reading through the article, I could not feel but all the medical scientists look at human body as if it a machine. Human body embodys energy by which human's biological cells work. The energy can be generated by mind, not just from foods. Weimar Institute receives patients whose doctors have given up treatments. But these patients find new life from the NEWSTART. You may not want to hear it, but, believe or not, it is true. There is a secrete in human body that modern medicine cannot find.
I am pretty sure Steve did not get my message.
There's an integrative cancer treatment center that is raising money for pancreatic research in Steve's honor here http://www.nhwellnesscenters.com/stevejobs/
Reply | Report Abuse | Link to thisThe email that started it all is pretty well written.
Kind of wish the stories were more specific.
I'm a survivor of a pancreatic mucin producing tumor similiar to Jobs' IPMN, called a Mucinous Cystic Neoplasm, diagnosed in 2005, surgery in early 2006, cancer free since then! But it was close, since it tested positive for CD10 expression, confirming it was precancerous. UCLA doctors said I had 2 weeks - 2 months before it'd have turned to cancer and become a regular adenocarcinoma. God blessed me and I thank Howard A Reber, Professor of Pancreatic Surgery at UCLA for saving my life.
Reply | Report Abuse | Link to thisDeborah Calvert, Newport Beach, California
There's a difference between a biopsy on an organ with tumor or a cancer and a biopsy on an organ not so.
Reply | Report Abuse | Link to thisRegardless of who cried, things like commencement addresses are often self-serving pronouncements and exaggerations. At the time Jobs was making a "seize the day" speech, he considered himself "cured" and as many cancer "survivors" do, he was pinning a ribbon on himself for fighting and beating cancer. My views come from my own research on prostate cancer, the only cancer I know of where they will do a biopsy and then tell you you can watch and wait and where there is ample accumulating evidence that possibly a biopsy and definitely surgery for a tumor with a low metastatic potential, itself, may be an important metastatic mechanism. Here are some plain language references you might begin with Googling : (1) "Old Ideas Spur New Approaches in Cancer Fight." Published: December 28, 2009 If you are watching and waiting read the article before you submit to another biopsy. Some excerpts: "Over and over, doctors and patients tell stories of injuries that seemed to spur a cancer. A blow to the breast, an operation, and suddenly cancer takes off. It may mean nothing, just an effort to explain the seemingly inexplicable. "... mathematical modeling indicates that surgery at the site of a dormant tumor can spur it to grow." "if wounding or inflammation has an effect, it happens only under unusual conditions and if tiny cancers are already present at the site of the wound." "Most likely, if there is an effect, it happens only if tiny cancers are already present at the site of the injury. " "It made her ask about biopsies ... “Frankly, this has not been studied extensively,” Dr. Polyak said. “People don’t like to bring it up.”" (2) From the Economist 12/11/2010: Better safe than sorry Medicine: A new type of needle provides a better way to collect samples from tumours, without the risk of spreading the cancer. (3) “Our findings suggest that promoting inflammation of the cancerous tissue – for instance, by performing prostate biopsies – may, ironically, hasten progression of metastasis,” said Karin. “We have shown that proteins produced by inflammatory cells are the ‘smoking gun’ behind prostate cancer metastasis. The next step is to completely indict one of them.”
Reply | Report Abuse | Link to thisI think it's absolutely important to highlight Mr. Jobs' decision to first try "alternative medicine" (which is another term for hoax medicine). Steve McQueen is another example of a desperate man who had money and an ego which tricked him into believing he'd found a way to beat the odds which were killing other victims. Both men made their living selling the not-quite real, Jobs was a master salesman and McQueen was a famous actor. It's worth mentioning because facing certain death pressures the victim to seek other kinds of unreality. There're plenty of charlatans out there ready to take your money or your insurer's money. Meanwhile: Science marches slowly but it does keep marching.
Reply | Report Abuse | Link to thisI'll second your statement about "injuries" triggering cancerous growths. 2 years ago, I (very slightly) scratched an itch under my right eye. That little scrape on the skin didn't heal: it started a growth which, within 2 months proved to be skin cancer. Before scratching: skin clear, after scratching: tumor appears. Three sessions of MOHS surgery removed all traces. Unpleasant but nothing compared to other surgeries.
Reply | Report Abuse | Link to thisBTW: another person I know waited 2 years before having her skin tumor looked at. She's undergone far more surgeries and still the doctors aren't sure she's cancer free. DO NOT WAIT to have suspicious lesions examined!
I learned also: I have "Celtic heritage" and that, in my 60s, makes me a prime candidate for MORE skin cancers. Whatever remains of my life: I must be on constant watch for any changes on my skin.
To update and verify parts of my speculation about Steve Jobs this medical journal report will show that a biopsy is not necessary to diagnosis an insulinoma in someone with SYMPTOMS. Jobs obviously had no symptoms and wanted to find out what the "shadow" was on his CT scan which was done to check for a recurrence of kidney stones. This case study the biopsy, while not causing metastasis, caused significant harm. http://www.contemporarysurgery.com/pages.asp?aid=321 "Is a DiagnosticTissue Biopsy Always a Good Idea?"
Reply | Report Abuse | Link to this"Celtic heritage"
Reply | Report Abuse | Link to thisTwice , the human model of cancer , the Celtic Curse , was mentioned in this conversation. Neuroendocrine cancer is very common in those with the Celtic Curse , excess iron .
"Iron overload in the endocrine glands"
Iron overload in the pancreas.
"MRI disclosed in 19 of 21 patients moderate to severe IO in the liver and spleen, in three of eight patients in the pancreas"
Iron chelating drugs are used in different cancers. One might wonder whether the underlying cause of cancer IS , as evidenced by recovery , iron excess ?
"NOVEL THIOSEMICARBAZONE IRON CHELATORS INDUCE UP-REGULATION AND PHOSPHORYLATION OF THE METASTASIS SUPPRESSOR, NDRG1: A NEW STRATEGY FOR THE TREATMENT OF PANCREATIC CANCER."
"IRON CHELATORS INDUCE UP-REGULATION AND PHOSPHORYLATION OF THE METASTASIS SUPPRESSOR, NDRG1"
"Doxorubicin (DOX) up-regulated mRNA levels of the iron-regulated genes transferrin receptor-1 (TfR1) and N-myc downstream-regulated gene-1 (Ndrg1). This effect was mediated by iron depletion, because it was reversed by adding iron and it was prevented by saturating the
anthracycline metal binding site with iron."
"Ndrg-1 is up-regulated in cells following iron (Fe)-depletion using Fe chelators"
"Ndrg-1 expression was demonstrated to be regulated by cellular iron levels and induced by iron chelators."
"Increased Ndrg1 expression following Fe chelation was related to the permeability and antiproliferative activity of chelators and could be reversed by Fe repletion."