Johns Hopkins scientists have developed a potentially
novel way to fight colorectal cancer using
tiny molecules to deliver potent barrages of radiation
inside cancer cells, unlike current treatments
that bind to the surface of cells and attack from the
outside and cause unwanted side effects.
In laboratory studies with normal and cancer cells,
the new radiation delivery system proved
able to specifically target colon cancer cells, and what
radiation is left over is likely to be easily
filtered out by the kidneys because the delivery system's
molecules are so small.
As reported online in PLoS One on Oct. 3,
colorectal cancer specialists John Abraham and
Stephen Meltzer, working with the notion that small
molecules generally make better treatment
packages, designed small bits of protein only 10 amino
acids long as the foundation for their drugs. By
contrast, antibodies used to deliver radiation or chemicals
can be more than 1,000 amino acids long.
The team attached radioactive phos-phorous, P32, as a
test of how well their peptides worked,
and "to our surprise, our first tests showed that cells
were ingesting these molecules, thus
transferring the radiation inside and killing them by
breaking up their DNA and proteins," Abraham
said.
While cautioning that the new radiation delivery
system is still far from ready for use in people,
Abraham noted that P32 gives off high energy that can
penetrate through 5 millimeters of human
tissue, making it a good candidate to tackle colon cancer
since colon cancer cells can often form large,
thick tumors into which drugs may not penetrate very well.
In addition, P32-labeled peptides may
serve another valuable use: to find small metastases or
recurrences of colon tumors while they are
still small enough to treat. Images of the body can be
taken of the labeled peptides as they bind,
revealing where stray tumor cells may be nesting.
Abraham, Meltzer and their team then designed and
tested a variety of P32 peptides on 18
normal and cancerous human cell samples. The most potent
peptide, MA5, could bind to
adenocarcinoma cells, which make up 95 percent of all colon
cancers, 150 times more strongly than
other cell types and be transferred inside cells within two
hours.
The research was funded by the National Cancer
Institute. Authors on the paper are Abraham,
Fumiaki Sato, Yulan Cheng, Bogdan Paun, Takatsugu Kan,
Alexandru Olaru, Zhe Jin, Jian Yang, Rachana
Agarwal, Stefan David, James Hamilton, Tetsuo Ito, Yuriko
Mori and Meltzer, all of Johns Hopkins.
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