The Deadly Secrets Of Pancreatic Cancer

Main Category: Pancreatic Cancer
Article Date: 27 Oct 2012 - 0:00 PDT Current ratings for:
The Deadly Secrets Of Pancreatic Cancer

A large-scale study that defines the complexity of underlying mutations responsible for pancreatic cancers in more than 100 patients was published in Nature.

The analysis represents the first report from Australia's contribution to the International Cancer Genome Consortium (ICGC), which brings together the world's leading scientists to identify the genetic drivers behind 50 different cancer types.

Pancreatic cancer has the highest mortality rate of all the major cancers and is one of the few for which survival has not improved substantially over the past 40 years. It is the fourth-leading cause of cancer death.

Professor Sean Grimmond, from the Institute for Molecular Bioscience (IMB) at The University of Queensland, and Professor Andrew Biankin, from The Kinghorn Cancer Centre at Sydney's Garvan Institute of Medical Research/ St. Vincent's Hospital led an international team of more than 100 researchers that sequenced the genomes of 100 pancreatic tumours and compared them to normal tissue to determine the genetic changes that lead to this cancer.

"We found over 2,000 mutated genes in total, ranging from the KRAS gene, which was mutated in about 90 per cent of samples, to hundreds of gene mutations that were only present in 1 or 2 per cent of tumours," Professor Grimmond said. "So while tumours may look very similar under the microscope, genetic analysis reveals as many variations in each tumour as there are patients.

"This demonstrates that so-called 'pancreatic cancer' is not one disease, but many, and suggests that people who seemingly have the same cancer might need to be treated quite differently."

Professor Biankin said such individual genetic diagnoses and treatments represent the future of healthcare. "In this study, we found a set of genes, the axon guidance pathway, that is frequently damaged in pancreatic cancer patients and is associated with a potentially poorer outcome for those patients. It is a new marker of pancreatic cancer that can be used to direct prognoses and treatments.

"'Personalised medicine', where the molecular profile of a patient is matched to the best treatment, is the way the world is moving for many diseases, not just cancer."

"The challenge now will be in moving from population healthcare and a 'one drug fits all' model to personalised healthcare. First we must take the time to develop the necessary genetic knowledge and implement health systems to translate that knowledge effectively."

Professors Biankin and Grimmond acknowledged the vital assistance of the Australian Pancreatic Cancer Genome Initiative, a network of more than 20 hospitals and research institutions Australia-wide, with over 200 members - surgeons, pathologists, nurses and researchers - that all contributed to the project.

They also collaborated with colleagues from the Baylor College of Medicine and The Methodist Hospital Research Institute in Texas, the Ontario Institute for Cancer Research, Johns Hopkins University in Maryland, the University of California San Francisco, the University of Verona, the Cambridge Research Institute and the Sanger Centre in the UK.

The ICGC project is being funded through $27.5 million from the National Health and Medical Research Council of Australia (NH&MRC), its largest-ever single grant. NHMRC Chief Executive Officer, Professor Warwick Anderson said that "NHMRC is proud to have been the major funding contributor to this research, and I am delighted that breakthroughs have been made in understanding the genetic basis of this disease.

"This positive outcome is evidence of NHMRC supporting the very best research and researchers, and the importance of our involvement in strong national and international collaborations.

"The ultimate goal of our funding is healthier citizens, both in Australia and overseas, and this research will certainly lead to a better understanding of this issue."

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our pancreatic cancer section for the latest news on this subject. FUNDING
As well as the NHMRC funding, we acknowledge the following additional funding support:
Commonwealth Department of Innovation, Industry, Science, Research and Tertiary Education (DIISRTE); Australian Cancer Research Foundation (ACRF); Queensland Government (NIRAP); The University of Queensland; Cancer Council NSW; Cancer Institute NSW; Avner Nahmani Pancreatic Cancer Research Foundation; R.T. Hall Trust; Petre Foundation; Jane Hemstritch in memory of Philip Hemstritch; Gastroenterological Society of Australia (GESA); American Association for Cancer Research (AACR) Landon Foundation – INNOVATOR Award; Royal Australasian College of Surgeons (RACS); Royal Australasian College of Physicians (RACP); Royal College of Pathologists of Australasia (RCPA).
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Heavy smokers, drinkers can face pancreatic cancer earlier in his life

Friday, October 5 HealthDay News)-drinkers and heavy smokers can develop pancreatic cancer at a younger age than other people, according to a new study.

The average age at which patients are diagnosed with pancreatic cancer is 72, according to the American Cancer Society.

But this study of more than 800 patients of pancreatic cancer that heavy smokers were diagnosed in above the age of 62 and drinkers at the age of 61 - a decade before the average age at the time of diagnosis.

Heavy smokers were defined as those who smoked more than one pack of cigarettes a day and drinkers were those who averaged three drinks per day.

The study also found drinkers were diagnosed with cancer of the pancreas at a younger age than those who drank other types of alcohol, such as wine or liquor from beer. But when the researchers took the amount of alcohol consumed in mind, the type of alcohol did not affect the age at diagnosis.

The good news was that they can reverse the harmful effects of heavy smoking and drinking. Ten years after renouncing their unhealthy habits, drinkers and former smokers did not have an increased risk of being diagnosed with cancer of the pancreas in an early age.

The study was published online on August 28 in the American Journal of Gastroenterology.

The findings could help determine at what age should begin detection of pancreatic cancer, once widespread screening is available.

"How to develop programs of research, an understanding of the influence of personal characteristics as the age of presentation is important to optimize the time of these projections," internal author of main study and gastroenterologist Dr. Michelle Anderson, Assistant Professor of medicine at the University of Michigan health system, said at a UMHS press release.

Although the study found associations between drinking, smoking and diagnosis of cancer of the pancreas at younger ages, did not demonstrate cause and effect relationships.

More information

The American cancer society has more about cancer of the pancreas.

Source: University of Michigan Health System, press release, October 01, 2012

Copyright © 2010 HealthDay. All rights reserved.

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Steve Jobs Faces Uphill Battle Against Cancer: Experts

This news article has expired. Below you will find a short description about the news article and comments that were left by CancerCompass users.

Prognosis for rare neuroendocrine disease is poor, doctors say

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Chemotherapy plus synthetic compound for pancreatic cancers

Human pancreas cancer cells dramatically regress when treated with chemotherapy in combination with a synthetic compound that mimics the action of a naturally occurring "death-promoting" protein found in cells, scientists at UT Southwestern Medical Center have found.

The research, conducted in mice, appears in today's issue of Cancer Research and could lead to more effective therapies for pancreatic and possibly other cancers, the scientists said.

"This compound enhanced the efficacy of chemotherapy and improved survival in multiple animal models of pancreas cancer," said Dr. Rolf Brekken, associate professor of surgery and pharmacology and the study's senior author. "We now have multiple lines of evidence in animals showing that this combination is having a potent effect on pancreas cancer, which is a devastating disease".

In this study, Dr. Brekken and his team transplanted human pancreatic tumors into mice, then allowed the tumors to grow to a significant size. They then administered a synthetic compound called JP1201 in combination with gemcitabine, a chemotherapeutic drug that is considered the standard of care for patients with pancreas cancer. They observed that the drug combination caused regression of the tumors.

"There was a 50 percent regression in tumor size during a two-week therapy of the mice," Dr. Brekken said. "We also looked at survival groups of the animals, which is often depressing in human therapeutic studies for pancreas cancer because virtually nothing works. We found not only significant decrease in tumor size, but meaningful prolongation of life with the drug combination".

The drug combination was also effective in an aggressive model of spontaneous pancreas cancer in mice.

The compound JP1201 was created in 2004 by UT Southwestern scientists to mimic the action of a protein called Smac. The scientists discovered Smac in 2000 and observed that this protein plays a key role in the normal self-destruction process present in every cell.

Cell death, or apoptosis, is activated when a cell needs to be terminated, such as when a cell is defective or is no longer needed for normal growth and development. In cancer cells, this self-destruct mechanism is faulty and lead to breaks in the cell-death cascade of events. The synthetic Smac, or Smac mimetic, developed at UT Southwestern inhibits these breaks, allowing the cell to die.

"In essence, we're inhibiting an inhibitor," Dr. Brekken said. "And we're allowing the apoptotic cascade to kick off, resulting in the death of cancer cells".

UT Southwestern scientists are using Smac mimetics in breast and lung cancer research, as well. Dr. Brekken said the next step is to develop a compound based on JP1201 that can be tested in humans in clinical trials.

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New drug substantially extends survival in pancreatic cancer

A new form of chemotherapy that destroys new blood vessels that grow around tumors has produced excellent results in a phase II trial of patients with inoperable pancreas cancer, scientists report at the 33rd Congress of the European Society for Medical Oncology (ESMO) in Stockholm.

European researchers led by Prof. Matthias Lhr from the Karolinska Institute reviewed the efficacy and safety of three different doses of cationic lipid complexed paclitaxel (EndoTAG-1) administered twice weekly, in combination with weekly infusions of gemcitabine, in comparison to gemcitabine alone, in 200 patients with pancreatic adenocarcinoma.

"EndoTAG consists of charged particles that bind preferentially to the fast-growing endothelial cells in new blood vessels being formed by tumors," Prof. Lhr explained. "The drug, paclitaxel, is then released and thus directly reaches an important target in tumors, i.e. the vessels. Paclitaxel itself is not very efficient in pancreratic cancer".

After following patients for a year, the scientists observed that therapy with such combination led to a substantially extended median survival time in comparison to standard treatment. Patients given gemcitabine alone survived on average 7.2 months, in comparison to up to 13.6 months for patients who received repeated doses of the combination (EndoTAG plus gemcitabine).

"These results are the best I have ever seen in palliative therapy in pancreas cancer," Prof. Lhr said. "The results are really excellent and a phase III study is in the making".

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Did you know?
A new form of chemotherapy that destroys new blood vessels that grow around tumors has produced excellent results in a phase II trial of patients with inoperable pancreas cancer, scientists report at the 33rd Congress of the European Society for Medical Oncology (ESMO) in Stockholm.

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Why Cancer Symptoms May Elude M.D.

FRIDAY, Feb. 24 (HealthDay News) -- Diagnosing cancer is more difficult in certain groups of patients, according to a British study.

Researchers analyzed data gathered from more than 41,000 patients with 24 types of cancer who were treated in 158 hospitals across England. They found that 77 percent of those who saw their family doctor about suspicious symptoms were referred to a hospital after only one or two consultations.

However, the study found that women, young people, non-white patients and patients with less common cancers were more likely to see their family doctor three or more times before they were referred to a hospital.

The researchers identified large differences in the promptness of family doctors in England to diagnose different types of cancer. Patients with symptoms of multiple myeloma, lung and pancreatic cancer required many more consultations with their family doctor before they were referred to a hospital, compared to patients with more common cancers such as breast, melanoma and testicular.

For example, almost 51 percent of patients with the blood cancer multiple myeloma required multiple visits to their family doctor before referral, compared with less than 8 percent of breast cancer patients.

Differences in the nature and characteristics of symptoms may explain why certain cancers are more difficult to diagnose, the researchers said. For example, multiple myeloma is especially difficult to diagnose because it mimics other conditions, while a breast lump may readily suggest cancer, the authors said.

They also said that doctors may be less likely to consider cancer in younger patients and may have communication difficulties with patients from different ethnic groups, which may explain why cancer diagnoses can take longer in these patients.

The study appears online Feb. 24 in The Lancet Oncology.

"These findings highlight limitations in current scientific knowledge," lead author Georgios Lyratzopoulos, of Cambridge University, said in a journal news release. "Medical research in recent decades has prioritized improving cancer treatments, but knowledge about the 'symptom signature' of common cancers and practical solutions on how best to diagnose them is still emerging."

Martin Guilliford, of King's College London, wrote in an accompanying editorial that the findings raise several questions that should be tested in future research.

He said some of those questions are: "Do modes of cancer presentation vary systematically between different groups of patients? Are (family doctors) more reluctant to refer young or non-white patients for investigation of possible cancer? Are participants in these groups less willing to accept a referral to investigate possible cancer?"

More information

The American Academy of Family Physicians has more about cancer diagnosis and tests.

SOURCE: The Lancet Oncology, news release, Feb. 21, 2012

Copyright © 2012 HealthDay. All rights reserved.

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Malaria drug for pancreatic cancer?

Researchers report they have shrunk or slowed the growth of notoriously resistant pancreatic tumors in mice, using a drug routinely prescribed for malaria and rheumatoid arthritis.

The pre-clinical results, which will appear in the recent issue of the journal Genes & Development and is currently published on its web site, have already prompted the opening of a small clinical trial in patients with advanced pancreas cancer, one of the deadliest and hardest-to-treat forms of cancer, said the investigators, led by Alec Kimmelman, MD, PhD, a radiation oncologist at Dana-Farber.

"We are seeing robust and impressive responses in pancreas cancer mouse models," said Kimmelman, whose laboratory specializes in studies of pancreas cancer, the fourth-leading cause of cancer death in the United States. The oral drug, hydroxychloroquine, is inexpensive, widely available, and causes relatively mild side effects, he said. A second, planned clinical trial will combine the drug with radiation.

"While these findings are indeed exciting and a cause for optimism, one needs to be mindful that so far the effects, while impressive, have only been shown in mice," said Ronald DePinho, MD, director of the Belfer Institute for Applied Cancer Science at Dana-Farber. "I eagerly await to see how the human studies will progress".

A new therapy avenue would be extremely welcome in pancreas cancer. The National Cancer Institute estimates that 43,140 people were diagnosed in 2010 and 36,800 died. Despite some recent gains with targeted molecular agents and combination regimens, only about 6 percent of patients live five years, and the median survival is less than six months.

Hydroxychloroquine is a form of the drug chloroquine, which is used to prevent and treat malaria and also prescribed for autoimmune diseases, including lupus and rheumatoid arthritis. These compounds have recently stirred much interest in cancer research, because they inhibit a process called autophagy (from the Greek for "self-eating") that is elevated in cancer cells.

Autophagy is present in normal cells as well, but at a much lower level. The process enables cells to break down and eliminate proteins, such as damaged cell membranes and worn-out organelles like mitochondria. But it is also a survival strategy. When nutrients are scarce, cells can digest and feed on their own non-critical proteins to avoid starvation.

Cancer cells also use autophagy to outwit chemotherapy therapy. Research has shown that cancer cells can activate this process in response to a variety of cancer therapys, allowing them to survive during the stress of treatment. But, as Kimmelman noted, autophagy can also be a cell-death mechanism. Cancer scientists are intensely studying ? and debating ? how to manipulate autophagy as a potential method to slow tumors' growth or make them more sensitive to other therapies.

In their research reported in Genes & Development, Kimmelman and his colleagues were stunned to find that autophagy was turned on at all times in pancreas cancer cell lines ? not just under conditions of stress, therapy or starvation. "This was a big surprise," he said. "These cells weren't deprived of nutrients; they were swimming in all the nutrients they could ever want." This suggested that for some unknown reason, pancreas tumors are highly dependent on autophagy, and therefore potentially uniquely good candidates for autophagy-inhibiting therapy.

In their next experiments, the team administered chloroquine to several different pancreas cancer cell cultures, and also tested its effects in three types of mouse models. In the laboratory cultures, they reported, the drug "markedly decreased" the growth of the tumor cells, showing that the cells were heavily dependent on autophagy to for continued growth.

In vivo testing involved three types of mouse models ? human pancreas cancer cells placed under the rodents' skin (xenografts); human cells injected into the animals' pancreases (orthotopic transplants); and a genetic model (mice bioengineered to develop native pancreatic tumors).

The response to chloroquine was "profound" in the xenograft models, Kimmelman said: All eight untreated mice died of their cancer within 140 days, while only one of eight treated mice had died by 180 days.

The drug's effects were less dramatic but still impressive in the orthotopic and genetic mouse models, the scientists said. The tumors that developed in the genetically pancreas cancer-prone mice were, like their equivalent in human patients, extremely resistant to all therapys. Among other properties, these tumors were embedded in tough, fibrous tissue that is difficult for drugs to penetrate.

Nevertheless, the researchers reported that chloroquine therapy as a single agent increased the rodents' survival by 27 days compared with untreated control mice. This is encouraging, Kimmelman commented, because even the newest targeted drugs aimed at pancreas cancer "don't have much effect in this genetic mouse model".

The Dana-Farber trial of hydroxychloroquine, led by Kimmelman and oncologist Brian Wolpin, MD, is designed to enroll 36 pancreas cancer patients in whom first- or second-line therapys have failed. The drug is taken in pill form twice a day. Results won't become available for at least a year, said Kimmelman.

Kimmelman said the next step will be to investigate the combination of hydroxychloroquine with radiation in patients with operable pancreas cancer.

"This is a very interesting and promising approach, attacking the Achilles' heel in pancreas cancer's defenses," commented Robert Mayer, MD, of Dana-Farber's Center for Gastrointestinal Oncology. "But it's too early to say whether hydroxychloroquine should be added to chemotherapy, and what the risks and benefits might be, so we want to examine it in a clinical trial".

Kimmelman's lab is also investigating other forms of cancer that might be good candidates for inhibition of autophagy by the drug. He said that their work, as well as recent findings from other labs, suggests that those cancers appears to be ones that are primarily driven by the KRAS oncogene ? as nearly all pancreatic tumors are.

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