In silico discovery of predictive biomarkers
The Biomarker Analysis Tool: Data mining on large cell panel screening data
A large cell panel screen was performed with an MDM2 inhibitor to find tumor cell lines responsive to treatment. In a subsequent analysis, we strove to identify gene expression or mutation patterns associated with drug efficacy.
The Biomarker Analysis Tool examines the correlation between the drug efficacy and the genomic signature of the tumor cell lines regarding mutations, gene expressions, or somatic gene copy numbers.
The results showed that tumor cell lines with high MDM2 expression were most susceptible to drug treatment. On the other hand, mutations of p53 correlated with resistance. The most relevant mutation position was identified as TP53 273Arg.
Taken together, when choosing cell lines and tumor models for further characterization of the MDM2 inhibitor, the p53 mutation status, as well as the MDM2 expression profile, will be important considerations.