Thursday, June 19, 2014

Irinotecan - Topoisomerase Poison

Easily the most stress of PY1 came from the Biochemistry Presentations.  Another group lab presentation, but instead of fun, herbal supplements, we talked about the way chemo and antiviral medications worked.  I greatly enjoyed the topic, but the level of difficulty increased dramatically.  My group was given irinotecan, a treatment for colorectal cancer.  Not a lot of jokes were going to be made in this one.

Irinotecan is a very interesting drug.  The molecule blocks the effects of Topoisomerase 1 and results in an accumulation of double strand breaks that leads to cell death.  Of the cancers, Topo1 increases the most in colorectal cancer, but it is being investigated for others as well.  Irinotecan acts as a prodrug for its active metabolite, SN-38, which undergoes glucuronidation and can become a part of enterohepatic recycling leading to extreme diarrhea.  The complexity of irinotecan showed up in every class during the spring semester.  Which was great, as I became an expert on the drug.

While other groups took the traditional lecture approach to the presentation, my group wanted to do something different.  We created a demonstration of Topoisomerase with rope, scissors and duct tape.  As DNA is copied for cell division, the unwinding of the helix increases the stress on the molecule upstream.  Topo1 releases that stress by cutting one strand of the DNA, allowing the molecule to unravel, and resealing the original cut.  Pretty simple idea, especially if you could have seen our demonstration.  We did do it, but due to snow delays only six people were in the room and I doubt anyone watched the video afterward.  However, it was a big hit with the professors and TAs as other people who weren't there came up and talked to me about it.

As I said, it was a group project with a great group of girls.  I do not want to take all the credit by posting it on her.  My job was the Mechanism of Action.  I chose it specifically because it generally received the most difficult questions from the feared professor.  Other than issues with the weather, our group nailed the presentation - possibly even the best of the semester.

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