New Radioactive Agents for Colon Cancer Work Inside Cells

Researchers have developed a potentially novel way to fight colorectal cancer utilizing tiny molecules to deliver potent barrages of radiation inside cancer cells, unlike existing 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 precisely target colon cancer cells, and what remains is likely to be easily filtered out by the kidneys because the delivery system's molecules are so small.

As reported in the October 3, 2007, issue of the journal PLoS One, Johns Hopkins University (Baltimore, MD, USA) colorectal cancer specialists John Abraham, Ph.D., and Stephen Meltzer, M.D., working with the theory that small molecules typically make better treatment vehicles--designed small pieces of protein, only 10 amino acids long as the foundation for their drugs. By contrast, antibodies used to deliver radiation or chemicals can be over 1,000 amino acids long.

The team attached radioactive phosphorous, 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,” Dr. Abraham said.

While cautioning that the new radiation delivery system is still far from ready for use in humans, Dr. Abraham noted that P32 gives off high energy that can penetrate through 5-mm of human tissue, making it a good candidate for fighting colon cancer since colon cancer cells can frequently form large, thick tumors into which drugs may not penetrate very well. Moreover, 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.

The investigators then designed and evaluated a variety of P32-peptides on 18 normal and cancerous human cell samples. The most potent peptide, MA5, was shown to be able to bind to adenocarcinoma cells, which make up 95% of all colon cancers, 150 times more strongly than other cell types and be delivered inside cells within two hours.


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