Navigation Links
Genetic Pathways to Curable and Incurable Forms of Pancreatic Cancer Identified

Pancreatic ductal adenocarcinoma is an almost uniformly fatal disease regardless of the stage at time of diagnosis. However, a small percentage //of patients develop a form of ductal adenocarcinoma associated with cystic lesions that can be detected earlier, is less aggressive and has a 50 percent long-term survival rate. Why cystic ductal pancreatic cancer behaves differently, despite carrying the same basic genetic mutations as the more common and deadly type of ductal pancreatic cancer, has long been a mystery. Now researchers at Fred Hutchinson Cancer Research Center have unlocked the genetic reason why.

Using unique mouse models to mimic the progression of both forms of human pancreatic cancer, researchers have discovered that a specific sequence of otherwise common genetic mutations is responsible for sending cells down the less-traveled path toward cystic pancreatic cancer versus the well-traveled route to the more fatal form of ductal pancreatic cancer.

Sunil Hingorani, M.D., assistant member of the Hutchinson Center's Clinical Research and Public Health Sciences divisions, led a study to be published in the March 12 issue of the journal Cancer Cell that explains this sequence and details why the cells behave differently.

"Although at their end stage the two different routes to ductal pancreatic cancer can look very much the same under the microscope, involve the same constellation of genetic events, and culminate in invasive and metastatic disease that can ultimately kill patients, one route is 100 percent fatal while the other is 50 percent curable," Hingorani said. "Until now we didn't understand why. What these studies suggest is that it's not just the total complement of mutations that determines the behavior of these cancers but also the sequence in which the mutations arise."

About 5 percent of all primary tumors of the pancreas, out of 40,000 annual new cases in the United States, arise from cystic t umors.

The findings reported in the journal by Hingorani and colleagues represent an accidental discovery. The researchers started out studying the common genetic pathways to pancreatic ductal adenocarcinoma in hopes of finding clues to developing early detection biomarkers and possible treatments to halt the progression of the disease. The work involved activating the pancreatic cancer oncogene called Kras and then selectively mutating tumor-suppressor genes such as p53, p16 and Dpc4 in different combinations.

In the mouse model, which Hingorani first developed while at the University of Pennsylvania, the combination of Kras and p53 led to the more deadly form of pancreatic ductal adenocarcinoma. Earlier studies by researchers in Boston also found the same association between Kras and p16. From studies of human cancers, it is known that mutations in Dpc4 can also occur, but they do so late in the course of disease progression. The current study showed that the combination of Kras and an early mutation of Dcp4, in which one copy of the suppressor gene is eliminated, lead to cancer by a different path, beginning with the creation of a distinct class of precancerous lesions in the ductal epithelium called mucinous cystic neoplasms (MCN). This initiates a process that results in the rarer but far less deadly cystic pancreatic cancer.

MCN lesions often are large enough to be detected early by MRI or CT scan and also to cause symptoms. The cells in this cancer also react differently to a key signaling protein, TGFb, which can induce cancer cells to change shape and become more mobile and invasive. It turns out that the cystic pancreatic cancer cells are resistant to these effects of TGFb and these types of cancers are also less likely to invade surrounding tissues and to metastasize, or spread, to other organs. These properties likely contribute to the improved survival seen with this form of the cancer, Hingorani said.

Conversely, the initial lesions that lead to the more common and deadly form of pancreatic ductal adenocarcinoma, called pancreatic epithelial neoplasms, are tiny enough to be undetectable until the disease has progressed to the point where survival is almost nil. Moreover, these cells appear to be highly sensitive to the tumor-promoting properties of TGFb and thereby manifest a more aggressive behavior.

"With accurate animal models of both forms of pancreatic ductal cancers now in hand, it should be possible to unravel the detailed mechanisms behind their distinct behavior and hopefully identify points of vulnerability in the more fatal form to improve survival," Hingorani said.

Source-Eurekalert
'"/>




Related medicine news :

1. Genetic Dentistry: Your Dentist may be able to grow you a new set of Teeth.
2. Genetic influence in menopause
3. Genetics and cholesterol levels
4. Genetics helps in attacking cancer
5. Genetic disorder related with sleep patterns
6. Genetic innovation
7. Genetic tests for cancer
8. Genetic indicates memory
9. Genetic mutation to the fountain of youth discovered
10. Genetic differences found between Male and Female brains
11. Alcoholism Influenced By Both Genetics & Family Environment
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:12/6/2016)... ... , ... TopConsumerReviews.com recently gave a best-in-class 5 star rating to SpinLife, a ... to people who need help getting around. For some, advancing age has led to ... rehabilitation after an illness or accident. There is a wide variety of scooters, from ...
(Date:12/6/2016)... California (PRWEB) , ... December 06, 2016 , ... "Add ... users to flicker, flash, and flare from clip to clip with high quality 4K ... , TransFlare 4K Jewel contains 44 lens flares filmed on the RED Dragon. Utilizing ...
(Date:12/5/2016)... ... 05, 2016 , ... What: Shriners Hospitals for Children, with the help of ... – using a video monitor and web-enabled camera. Santa visits with children through Dimension ... a Christmas Wonderland, which is where the video connection to the North Pole will ...
(Date:12/5/2016)... ... December 05, 2016 , ... ... Surgery, is excited to announce the arrival of the newest Sciton laser in ... the ability to use tunable non-ablative and ablative wavelengths for exceptional results. Outperforming ...
(Date:12/5/2016)... , ... December 06, 2016 , ... For many years, ... poetry , both thick and thin. The beauty of the Lithuanian language ... Publishing). , In this poetry book, Zubinas lyrically explores all aspects of a living, ...
Breaking Medicine News(10 mins):
(Date:12/5/2016)... , Dec. 5, 2016   Lexicon Pharmaceuticals, ... results today from a Phase 2 clinical study of ... Lexicon in collaboration with JDRF, the leading global organization ... of this Phase 2 clinical trial, which randomized a ... of a once-daily 400 mg dose of sotagliflozin compared ...
(Date:12/5/2016)... , December 5, 2016 According to ... Treatment modalities (Chondrocyte Transplantation, Growth Factor Technology, Tissue Scaffolds, Cell-free composites), ... by MarketsandMarkets, the market is projected to reach USD 779.8 Million ... CAGR of 13.5% during the forecast period of 2016 to 2021. ... ...
(Date:12/5/2016)... PORTLAND, Oregon and PUNE, India ... a new report by Allied Market Research, titled, "Global Cancer ... the global revenue of cancer biomarkers market is projected to ... at a CAGR of 13.3% from 2016 to 2022. Omic ... share in 2015 and is expected to maintain its dominance ...
Breaking Medicine Technology: