Compounds (yellow) bind to the enzyme (in purple & blue) in symbiotic gastrointestinal bacteria blocks the reaction that leads to side effects and lessens toxicity of anticancer drug CPT-11 (Bret Wallace, Matt Redinbo)
Big discovery, small world
It’s a classic case of the title not telling the whole story.
“Alleviating Cancer Drug Toxicity by Inhibiting a Bacterial Enzyme” is the technical title of the study that appeared in the November 2010 issue of the prestigious journal, Science.
But it’s the acknowledgement at the end of the article that hints at the personal stories behind the research: “The authors remember Lisa Benkowski and Stacey Micoli, for whom CPT-11’s efficacy was limited by its toxicity.”
CPT-11, or Irinotecan, is a drug used to treat colon cancer and other solid tumors. While it has proven a valuable tool, CPT-11 can also cause severe diarrhea, which limits the dosage patients can tolerate.
The Science study’s senior author, UNC chemistry department professor and chair Matt Redinbo, had lost a colleague, Lisa Benkowski, to colon cancer in 2003. First author Brett Wallace lost a lifelong family friend, Stacey Micoli, to a rare form of ovarian cancer in 2007. Both women had taken CPT-11, but had to stop because of its side effects.
Redinbo, also a member of the Lineberger Comprehensive Cancer Center, began working on ways to improve the drug’s effectiveness several years ago; Wallace chose to work on the CPT-11 project after joining Redinbo’s lab as a graduate student in 2007.
But it wasn’t until late 2008 that the two shared their personal reasons for their strong interest in the work.
Redinbo explains. “When Bret joined the lab, I didn’t tell him right away why I was so interested in this project. Students work very hard, and I don’t want to make them anxious about whether or not an experiment would work.” When the research showed promise, Redinbo shared his story with Wallace.
Wallace says, “I listened to Matt’s story and then told him I had a personal story to tell him about why I wanted to work on this project. I hadn’t said anything earlier because I didn’t want him to think I was interested only because of my personal connection.”
Redinbo says he was stunned. “The odds are incredibly small of two people coming together from different backgrounds, with the same personal experience with someone they knew, and then having the opportunity to address scientifically that side effect.”
The common connection charged the team’s science and motivated their careful review of data and results, which point in a promising direction for potentially eliminating CPT-11’s debilitating side effects.
Watch video of Redinbo and Wallace describe the personal side of their research.
Listen to an interview with Stacey Micoli’s mother, Liz, that include her thoughts on the promise of this research.