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The 4% Solution
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Researchers
at the Stehlin Foundation have developed a way of speeding
up the process of testing anticancer drugs. An in vitro system
of 8 cell lines containing blood serum unique to the human
body is saving time and money as researchers race to find
treatments for cancer. Camptothecins are effective at inhibiting
the growth of all human tumors and eradicating some cancers
completely in the lab and in the nude mouse modeling system.
However, in the human body, human serum albumin (H.S.A.) neutralizes
some of the anticancer activity of camptothecins, reducing
their efficacy.
“Human serum albumin,” says Dr. Beppino Giovanella,
“reduces the camptothecins ability to treat tumors in
the human body. Every person has H.S.A. So, we’re looking
for the camptothecin compound that is not neutralized by H.S.A.
while continuing to eradicate tumors. With the growth of these
cell lines, we’re eight steps closer to finding it.”
Camptothecins are tremendously effective at treating human
tumors in the laboratory. 9-Nitro-Camptothecin (9-NC), developed
at Stehlin and marketed as Rubitecan by SuperGen, successfully
treats every form of cancer it has ever met.
“We’re able to cure cancer in the lab,” says
Stehlin Laboratory Supervisor Dana Vardeman. “Treating
and curing it inside our bodies is much more difficult. Our
bodies have a number of protective mechanisms that turn out
to be self-defeating when it comes to allowing medicines to
work.” One of the body’s protective mechanisms is
“human serum albumin.” “The first problem,”
explains Dr. Giovanella, “is that H.S.A. reduces the
effectiveness of camptothecins. The second problem is that
the nude mouse modeling system does not reflect the concentration
of H.S.A. found in the human body.” Earlier this year,
the researchers at the Stehlin Foundation began cultivating
cell lines with a 4% H.S.A. solution. “These cell lines,”
says Vardeman, “have become the first stop in the testing
cycle. After Dr. Cao’s team synthesizes a new camptothecin
compound, we run the derivative through a round of in vitro
testing with these 8 cell lines.” Dr. Giovanella outlines
the process: “If a camptothecin compound is effective
against tumors in the H.S.A. 4% solution, we pass it along
to additional in vivo modeling systems. If a potential anti-cancer
drug shows no activity in the H.S.A. cell lines which mimic
the human body, we know we don’t need to test it any
further.” The development of the 8 cell lines has been
a team project involving many researchers at the Stehlin Foundation.
"We continue to build on the successes of a team that
has served together for decades," says Bobby Anderson.
"Being able to use these 8 cell lines to immediately
knock out camptothecin compounds is a terrific boost in our
research process. It narrows the scope of possibilities, and
it does it quickly". Research is about expanding possibilities
and narrowing probabilities. While searching for treatments,
the Stehlin researchers explore every possibility available.
Once they begin focusing on a probability, however, the narrowing
process begins.
"The sooner we know whether a camptothecin derivative
will stand up to H.S.A., the closer we get to treatments for
human cancers,"says Dr. Giovanella. "These cell
lines accelerate the process for us dramatically." "It's
a huge benefit," agrees Bobby Anderson. "We're able
to test more compoundsmore quickly at a lower cost."
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