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Discussion
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Dr Quan-Yang Duh (San Francisco, CA): Very nice presentation and very exciting stuff. I sort of see this as similar to the thyroid cancer genome study.
Mitotane has been around for a long time. Our experience has been that there are some patients for whom it worked well, but in most patients it actually didn’t work. I assume that some of the patients that you have in this series had Mitotane. Have you looked at those who have taken Mitotane, and then compared responders to non-responders, to see where they actually come out different?
Dr Mark Cohen: For the TCGA, actually, the tumors were taken at the time of initial surgery, so it was likely prior to any Mitotane exposure. We have not looked at that specifically to see the effects of Mitotane on these pathways, especially in patients who have re- curred after Mitotane therapy. That’s something we certainly could do.
Dr Quan-Yang Duh (San Francisco, CA): It’s more of a question of whether you can predict which patient you should put on Mi- totane.
Dr Mark Cohen: I think that’s certainly a possibility. In other cancers we have shown that doing the genetic analysis
pre-treatment allows you to see which pathways are going to be susceptible. If it is not susceptible where Mitotane is targeting, then it’s probably not going to work. We have seen that with melanoma and some other types of tumors. That’s certainly some- thing that we will plan to do at some point.
Dr James Howe (Iowa City, IA): Mark, this is great work, and hopefully this will lead to some translational improvements in the care of these patients. You focused on 10 or 20 genes that you showed us, but I’m sure you had hundreds or even thousands of differentially expressed genes. How did you decide to just look at those?
Dr Mark Cohen: What we initially did was to look at level of expression as some cutoff for what we are interested in, in terms of genes of interest. So all of these that were of interest had modu- lation of at least 5- to 10-fold over normal. That narrowed it down from a larger pool to a much smaller pool. Then we looked at these high-modulation genes and whether they were increased or de- creased as our key targets to follow.