News Story La Jolla News, July 22, 2004
SKCC Makes Special Delivery: New Discovery Enables
More Precise Aim to Kill Cancer Cells
By Tanya Kurland
Village News
A breakthrough discovery by Sidney Kimmel Cancer Center (SKCC)
scientists will allow radiation therapy to kill cancer cells without
harming normal tissues, taking treatment to a much higher level of
safety and effectiveness.
The findings were published in a June 10 article in the scientific journal
Nature titled "Subtractive proteomic mapping of the endothelial
surface in lung and solid tumors for tissue-specific therapy" by Dr.
Jan E. Schnitzer, the cancer center's scientific director.
"It is as if we identified a ZIP code fo the cancer and can now mail
nearly all the drug to that ZIP code exclusively to increase tumor
destruction, while eliminating side effects from these powerful toxic
agents," Schntizer said.
Scientists focused on getting drugs to the tissues that need them, while
avoiding those that do not. This problem is acute in cancer therapy,
in which the drugs that kill tumors may also be highly toxic to non-cancerous
tissues.
In what they describe as a "systems biology" approach to the problem,
the researchers have identified a small subset of proteins in the endothelium--the
complex tissue that lines the walls of blood vessels--that are found
at the blood-tissue interface and which are therefore accessible to
drugs injected intravenously.
The team identified one single protein of the million or so in the body
that can be used to target a drug to travel freely into a solid, cancerous
tumor. The antibody developed can attach itself to that protein and
deliver traditional radioactive or chemotherapeutic drugs to the tumor
blood vessels, and then inside the tumor to kill the cancer.
The study showed that rats with advanced lung cancer only days away from
death had a 90 percent survival rate. In the past, the markers for
cancer tissue were acquired one at a time and about one per year. Now,
through the science of genomics, hundreds of new markers are acquired
for cancer every year.
Eight proteins never before found in tumor vasculature were identified
in this study, and dozens more that can serve as unique biomarkers
and therapeutic transport agents are expected to be identified, Schnitzer
said. These biomarkers also exist in human tumors.
"The use of these antibodies will revolutionize cancer imaging and therapy,"
said Dr. Albert B. Deisseroth, SKCC president and chief executive.
"The amount of drugs that reach the cancer tissue with these targeting
antibodies is 150 times higher than can be achieved by conventional
cancer treatments used today."
The findings will make cancer treatment safer, less expensive and less
disruptive to daily life than ever before. The discovery is not restricted
to radiation or chemotherapy and can work for lung, breast, kidney,
liver, colon, brain and prostate cancers as well as metastatic lesions.
While this breakthrough is very promising, it needs to be tested more
extensively in humans before its true clinical value will be known,
Schnitzer said.
The next phase will be applying this research to humans by peforming
whole-body clinical imaging studies directly on patients to find out
how many
of these proteins are there and how specific they will be for the solid
tumor in any given individual patient. The hope is that the same rapid
and specific targeting to solid tumors will be visualized in human
patients as has been imaged in the rat tumor models.
"Once we see the targeting profile for each antibody and determine which
protein target is most specific in humans, then we can rapidly proceed
with confidence to therapy," Schnitzer said.
Schnitzer is also the author of "Direct proteomic mapping of the lung
microvascular endothelial cell surface in vivo and in cell culture,"
which appeared online July 19 in the scientific journal Nature Biotechnology.
The article describes related findings of previously unidentified proteins
exposed on the surface of blood vessels in lung tissue, allowing the
targeting of various therapies selectively to lung tissue without harming
other body tissues.
It has been establlished that many of these proteins are expressed in
human tissues similarly. The protein mapping was accomplished in vivo,
using tissue extracted from actual tissue of rat lungs, rather than
in vitro, using tumor tissue cultured in the laboratory, which is more
common.
Lung cancer, now the leading cause of cancer death among men and women
in the U.S., is very resistant to chemotherapy, making all forms of
metastatic lung cancer incurable by chemotherapy. New approaches for
treatment and methods of detecting lung cancer before it spreads are
urgently needed to control this disease, Deisseroth said.
Since being establlished in 1990, the San Diego-based nonprofit Sidney
Kimmel Cancer Center, 10835 Altman Row, has been dedicated to the development
of advanced biological cancer treatments.
For more information visit www.skcc.org or call (858) 410-4212.
