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Tales of the 'Trojan horse drug' and the
Diagnosed with an extremely aggressive form
of cancer called anal sac adenocarcinoma, Oscar's future seemed bleak. Bedridden and
unresponsive to chemotherapy or radiation, he would be lucky to survive three months. But
thanks to an innovative new drug treatment, Oscar's cancer receded and he was walking
again within two weeks. Oscar's recovery was extraordinary enough, but his case was
unusual for another reason. Oscar is a Bichon Frise, who scientists reporting here today
at the 237th National Meeting of the American Chemical Society call "the Miracle
Dog." Joseph A. Bauer, Ph.D., and colleagues described promising results with a drug
called nitrosylcobalamin (NO-Cbl) in battling cancer in Oscar and three other canines
without any negative side effects. While it gives profound hope to dog owners, NO-Cbl also
points to a powerful new cancer treatment for humans one that infiltrates cancer
cells like a biological Trojan horse. "We are one of the few research groups that is
offering to treat dogs with cancer that otherwise have no hope," Bauer said.
"With no other options available, most people in this situation opt to euthanize so
that their pets don't go through the pain of disease and trauma of surgery."
About six million dogs are diagnosed with
cancer each year in the United States. According to the National Cancer Institute (NCI),
pets with cancer provide a win-win opportunity for cancer researchers. Scientists can
study new cancer treatments in animals other than lab mice. And pets get access to new
treatments that provide hope and in instances like NO-Cbl, additional time. Bauer put it
this way: "The beauty of using a dog or a cat to test a cancer drug is two-fold.
First, the animal can get the benefit of the most up-to-date drug in cancer medicine.
Second, the NCI gets data on pets that are exposed to the same environmental factors their
owners are. They breathe the same polluted air and drink the same polluted water that you
and I do every day. If you can find an agent to treat cancer that occurs in a dog with
success, there is a higher likelihood that you can take that to the human population and
have a much higher response rate than with mice."
Although NO-Cbl has been used in only a few
dogs, daily treatments have led to promising results in each case. "In all four dogs,
there has been a significant reduction in tumor size without any toxic side
effects or discomfort," says Bauer. Oscar was the first success story. Since
then, Bauer has treated two other dogs. A six-year old golden retriever named Buddy was
unable to walk due to a spinal tumor pinching essential nerves leading to his right hind
leg. After nine months of daily NO-Cbl treatment, Buddy's tumor shrank by 40 percent and
he was going on two mile walks. A 13-year-old female Giant Schnauzer with inoperable
thyroid carcinoma also showed tumor reductions of 77 percent in less than 10 weeks.
"Our case studies demonstrate anti-tumor efficacy with limited toxicity to normal
tissues," Bauer added. "NO-Cbl sensitizes multidrug-resistant cancer cells to
the antitumor effects of several different drugs, so it may be valuable when utilized in
combination regimes," he added.
The drug targets cancer cells with
"biological Trojan horse technology." Cells have receptors for vitamin B12 on
their outer surface. The receptors serve as docking ports where molecules of the vitamin,
essential for cells to divide and multiply, attach and then enter the cell. In order to
divide at their abnormally rapid pace, cancer cells grow extra B12 receptors 100
times more than normal cancer cells.
Scientists have been trying since the 1950s to exploit that vulnerability and make
B12-based drugs that attach to the receptors, sneak into the cell, and deliver a knock-out
dose of medication.
Bauer and his colleagues from the Cleveland
Clinic attached nitric oxide (NO) molecules to vitamin B12. NO kills cancer cells. The B12
acts as the Trojan horse, easily slipping into cancer cells. The
subsequent release of toxic NO kills the cancer cells from within. The team's goal
is to successfully treat 10 dogs with NO-Cbl and slingshot the drug into human use as soon
as possible. Because of the genetic similarity between dogs and humans, Bauer says his
approach should have a much better chance of getting through the FDA's strict drug
approval chain. But Bauer stresses he wants to get the NO-Cbl dog treatment approved, as
well. "I'm committed to the animals, and my goal would be to do a dual clinical
trial, Phase One human and Phase One dog," says Bauer. Oscar is still alive and well.
Today, Bauer is treating another Golden Retriever named Haley with a spinal tumor.
"This is one of the most rewarding things I've ever done in my life," says
Bauer, the owner of a two-year old Beagle. "It gets boring working in the lab, but to
see the fruits of your labor in a positive outcome like this and to know you're
responsible in some small way, that's pretty cool."
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