We have generated a cell line that is resistant to drug A. We now want to check for the DRI to compare the parental cell line (sensitive to drug A) to the resistant cell line. I have come across several papers listing DRI=IC50 of resistant/IC50 of sensitive. Does it matter if the IC50 of parental is achieved at 48 hours, but the resistant cell line at 72 hours? Example: 1 micromolar of drug A induces 50% growth inhibition 48 hours post-treatment in parental cell line; however, 20 micromolar of drug A induces 50% growth inhibition 72 hours post-treatment in the resistant cell line. Does that mean that DRI=20? or should the IC50 be obtained at the same timepoint hence, I should increase the concentrations used?
I appreciate your help.
Best,
Patrick
I am sending you an article that will provide mechanisms to calculate the drug resistance index in oncologyz
Drug Resistance Index(DRI) should be comparable across time and location so that it can be used to measure changes in drug effectiveness over time across hospitals, regions, states or countries.
DRI should be calculated with minimal data requirements that include the maximum level of detail (disaggregated by month or date, and by patient location). Calculation involves two major components: proportion of non-susceptible isolates and weighted antibiotic use.
DRI needs to be calculated from IC50 values obtained at the same timepoints. Consequently, actual DRI in your example would be higher than 20, because IC50 = 20 uM at 72 hrs in resistant cell line would likely correspond to IC50 > 20 uM at 48 hrs.
I'm also developing resistant cell line, but what I have seen is that we have to set the time dependent exposure prior setting the dose dependent treatment to establish a resistant cell line from parental. And for calculating calculating DRI the exposure time must be same, as because the effect of treatment in parental cells will be more than that of the resistant cells in same time period.
If you have already came with a solution for your question. Kindly let me know. Thank you
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