Note for: A Proposal Regarding Reporting of In Vitro Testing Results
Note for: A Proposal Regarding Reporting of In Vitro Testing Results
Doi: 10.1158/1078-0432.CCR-13-0043
Failure to translate to clinical research examples;
Sorafenib
Vorinostat
Metformin
They ask reviewer to limit the publications which reported the concentrations were not related to clinical level, to prevent the failure rate at the clinical levels.
The key point for the successfulness in term of translation from in vitro to clinical –
Testing with multiple cell lines
Giving wide variation of sensitivity
Only small portion of cell will be extremely sensitive at very low concentration
This subgroup has special molecular feature which is targetable for particular drug
Suggestion
Cells – heterogeneity
Test with many different types of cells
Picking up the cell with show sensitivity with very low drug concentration
Finding feature at the molecular level and tracing back to clinical level
How to get rid of bad data
Author proposed “desk reject” the MS which the concentrations are not reliable
For example;
sorafenib if report > 1 uM
metformin > 50 uM
vorinostat > 1uM
Criteria for reviewers
Paying attention to clinical relevance concentration – look at the reference
Rejecting MS which targeted agents having exceed concentrations (>10 folds, for example) at which agents effective against cell line expressing agent’s molecular target
WT – IC50 – 10 uM
KO of target – IC50 – 100 uM
If testing the unknown cell line – then – the concentration should not more than 100 uM, for example
Reject the MS which concentration is above clinically achievable drug levels
MS describing in vitro testing of targets with high protein binding adjust for low serum versus plasma protein conc. – check whether the concentration is clinically relevance
Exception
Metabolite is very active and achieve sufficiently high levels in patients, for example
References should be included in the study if the criteria is not met above
Comments
Post a Comment