Hi!
I am testing a new compound on colorectal cancer cell lines and I want to compare it's efficacy with the standard drug utilized in the treatment, which is the 5-FU. What concentrations should I use? I am using plasmatic concentrations found in blood samples collected from patients in treatment 2-3 hours after the infusion, are those concentrations considered clinically relevant?
Thanks in advance.
I think you should determine the IC50 with different exposure times: there is no real correlation between drug concentration in plasma and atitumour activity.
You may also want to test your compound in FU-resistant cell lines.
Then move to animal models.
Your approach makes sense to me; however, your cell line would have the luminal side exposed to the drug, whereas in the patient the basolateral side would be exposed to the drug if infused. I wouldn't assume this difference is insignificant, but I'm not sure how you would correct it other than using transwells. Probably most importantly, cell lines seem to poorly reflect tissue in its native environment. It might be more useful to take colon cancer directly from a rodent and grow those cells, or better yet, obtain some human colon cancer tissue from biopsies and grow that for testing.
I think its better to do a dose response of your compound as well as 5-FU and compare the IC50s. Then you can move to other cell lines or animal models.
Hope it is useful
Nagaraj
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