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 May 16, 2005
Scientists Seek Ways to Alter Colon Cancer Drug's Severe Side Effects
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An effective colon cancer drug's side effects are sometimes so severe it can't be used, and scientists are hopeful their new findings will help alter the drug's formula to make it tolerable to more people.

A team of scientists at the Weizmann Institute of Science, working in collaboration with scientists at St. Jude Children's Research Hospital in Memphis, Tenn. investigated the side effects of the drug CPT-11, an FDA-approved colon cancer medication. The researchers noticed that the side effects, which include nausea, vomiting and diarrhea, seemed similar to those experienced by some users of Alzheimer's drugs, and this led them to suspect an enzyme similar to the one in Alzheimer's might also be evident in reacting with CPT-11.

The drug is known as a prodrug, according to Weizmann Institute scientists Joel Sussman, Dr. Michal Harel and Israel Silman. This means that in order for it to become effective, it actually undergoes a molecular change after being injected in the body. The enzyme that initiates the change is known as acetylcholinesterase (AChE), and this may be what brings about the severe side effects.

"The enzymes are like locks made by the same locksmith, but varied slightly to open with different keys," Sussman said in a statement. "The cancer drug fits AChE like a key that slides in part way, but won't turn," he concludes.

The next step is to alter the delivery molecule to develop a better fit, the researchers say.


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