Drug Salirasib Doubles Life Expectancy for
Pancreatic Cancer Patients in Clinical Trials
Innovative TAU research holds promise for a broad
range of human disease
This picture shows the pancreas, common bile duct, and small intestine.
Read more below.
July 22, 2009 – One of the fastest cancer killers –
pancreatic cancer – is seeing its devastation slowed tremendously. The
drug compound Salirasib has passed Phase I/II clinical trials and almost
doubled the life expectancy of patients.
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.
This new hope comes from the lab of Professor Yoel
Kloog, dean of Tel Aviv University's Faculty of Life Sciences. His drug
compound Salirasib is given in combination with gemcitabine, the
standard drug used to combat pancreatic cancer.
"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.
A close up of the area shown in purple in
this drawing is at the top of the page.
The pancreas is a
gland behind your stomach and in front of your spine. It produces juices
that help break down food and hormones that help control blood sugar
levels. Cancer of the pancreas is the fourth-leading cause of cancer
death in the U.S. Some risk factors for developing pancreatic cancer
include
Pancreatic cancer
is hard to catch early. It doesn't cause symptoms right away. When you
do get symptoms, they are often vague or you may not notice them. They
include yellowing of the skin and eyes, pain in the abdomen and back,
weight loss and fatigue.
Also, because the
pancreas is hidden behind other organs, health care providers cannot see
or feel the tumors during routine exams. Because it is often found late
and it spreads quickly, pancreatic cancer can be hard to treat. Possible
treatments include surgery, radiation and chemotherapy.
About
The Pancreas
The
pancreas
is a
gland
located deep in the
abdomen
between the stomach and the spine (backbone). The
liver,
intestine,
and other organs surround the pancreas. (See picture at top of page)
The pancreas is
about 6 inches long and is shaped like a flat pear. The widest part of
the pancreas is the head, the middle section is the body, and the
thinnest part is the tail.
The pancreas makes
insulin
and other
hormones.
These hormones enter the bloodstream and travel throughout the body.
They help the body use or store the energy that comes from food. For
example, insulin helps control the amount of sugar in the blood.
The pancreas also
makes
pancreatic juices.
These juices contain
enzymes
that help digest food. The pancreas releases the juices into a system of
ducts
leading to the
common bile duct.
The common bile duct empties into the
duodenum,
the first section of the small intestine.
