Every year, 42,000 Americans are diagnosed with pancreatic cancer. Few live very long, and less than 5% are still alive five years after diagnosis.
There’s new hope, though, from the lab of Prof. Yoel Kloog, dean of TAU’s Faculty of Life Sciences. His drug compound Salirasib has shown positive results against pancreatic cancer and recently passed Phase I/II clinical trials. The drug, given in combination with gemcitabine, the standard drug used to combat pancreatic cancer, almost doubled the life expectancy of those who received it.
“In our study, the mean survival of pancreatic cancer patients was 10.8 months — better by far than the 6.2 months with gemcitabine alone,” says Prof. Kloog, who recently presented the results to a meeting of the American Society of Clinical Oncology. His basic research offers the promise of a weapon to attack a broader range of mankind’s most prevalent diseases, including lung, prostate and breast cancers as well as diabetes.
Blocking the Ras protein
Salirasib works by inhibiting a protein called Ras, which is known to be abnormally activated in one-third of human cancers. In cancer of the pancreas, mutant forms of Ras are found in up to 90% of all tumors. Salirasib’s basic component, FTS, works to block the formation of cancer-promoting Ras nanoclusters, thus blocking a cascade of biochemical signals known as the “Ras signaling pathway” that allow Ras to wreak havoc on the body.
Early in the 1990s, many drug developers chased after a mechanism to inhibit Ras by targeting enzymes that modify it, but they were unsuccessful. “The major developers gave up, claiming Ras is not targetable,” says Prof. Kloog, “but our concept takes a different approach. Now that we’ve shown it works in human subjects, I am definitely excited — no doubt about it.” Prof. Kloog developed the Ras antagonist more than 15 years ago.
No toxic side effects
In the latest study, researchers tested for both toxicity and effectiveness. They gave 19 patients with advanced pancreatic cancer daily doses of salirasib along with a standard gemcitabine regimen. Salirasib was well tolerated by the patients, and they surpassed on average the number of months they would have lived on gentamiacine alone. There were no toxic side effects, such as heart or lung ailments. Tumor biopsies showed a significant reduction in Ras levels, suggesting that the drug is inhibiting the action of Ras in the tumor itself.
For this study, Salirasib was licensed by Concordia Pharmaceuticals, which collaborated with the Memorial Sloan Kettering Cancer Center, Johns Hopkins, the M.D. Anderson Cancer Center and other institutes in the United States.
If Phase II/III trials are successful, Prof. Kloog’s drug will be the first successful Ras antagonist known to medical science. Salirabib could be medically available in as little as two years.
Pancreatic cancer is a disease in which malignant (cancer) cells form in the tissues of the pancreas.
The pancreas is a gland about 6 inches long that is shaped like a thin pear lying on its side. The wider end of the pancreas is called the head, the middle section is called the body, and the narrow end is called the tail. The pancreas lies behind the stomach and in front of the spine.
Smoking and health history can affect the risk of developing pancreatic cancer.
Anything that increases your risk of getting a disease is called a risk factor. Having a risk factor does not mean that you will get cancer; not having risk factors doesn’t mean that you will not get cancer. People who think they may be at risk should discuss this with their doctor. Risk factors for pancreatic cancer include the following:
Certain hereditary conditions, such as hereditary pancreatitis, multiple endocrine neoplasia type 1 syndrome, hereditary nonpolyposis colon cancer (HNPCC; Lynch syndrome), von Hippel-Lindau syndrome, ataxia-telangiectasia, and the familial atypical multiple mole melanoma syndrome (FAMMM).
Chest x-ray: An x-ray of the organs and bones inside the chest. An x-ray is a type of energy beam that can go through the body and onto film, making a picture of areas inside the body.
Physical exam and history: An exam of the body to check general signs of health, including checking for signs of disease, such as lumps or anything else that seems unusual. A history of the patient’s health habits and past illnesses and treatments will also be taken.
CT scan (CAT scan): A procedure that makes a series of detailed pictures of areas inside the body, taken from different angles. The pictures are made by a computer linked to an x-ray machine. A dye may be injected into a vein or swallowed to help the organs or tissues show up more clearly. This procedure is also called computed tomography, computerized tomography, or computerized axial tomography. A spiral or helical CT scan makes a series of very detailed pictures of areas inside the body using an x-ray machine that scans the body in a spiral path.
MRI (magnetic resonance imaging): A procedure that uses a magnet, radio waves, and a computer to make a series of detailed pictures of areas inside the body. This procedure is also called nuclear magnetic resonance imaging (NMRI).
Endoscopic retrograde cholangiopancreatography (ERCP): A procedure used to x-ray the ducts (tubes) that carry bile from the liver to the gallbladder and from the gallbladder to the small intestine. Sometimes pancreatic cancer causes these ducts to narrow and block or slow the flow of bile, causing jaundice. An endoscope (a thin, lighted tube) is passed through the mouth, esophagus, and stomach into the first part of the small intestine. A catheter (a smaller tube) is then inserted through the endoscope into the pancreatic ducts. A dye is injected through the catheter into the ducts and an x-ray is taken. If the ducts are blocked by a tumor, a fine tube may be inserted into the duct to unblock it. This tube (or stent) may be left in place to keep the duct open. Tissue samples may also be taken.
Percutaneous transhepatic cholangiography (PTC): A procedure used to x-ray the liver and bile ducts. A thin needle is inserted through the skin below the ribs and into the liver. Dye is injected into the liver or bile ducts and an x-ray is taken. If a blockage is found, a thin, flexible tube called a stent is sometimes left in the liver to drain bile into the small intestine or a collection bag outside the body. This test is done only if ERCP cannot be done.
- Biopsy: The removal of cells or tissues so they can be viewed under a microscope by a pathologist to check for signs of cancer. There are several ways to do a biopsy for pancreatic cancer. A fine needle may be inserted into the pancreas during an x-ray or ultrasound to remove cells. Tissue may also be removed during a laparoscopy (a surgical incision made in the wall of the abdomen).