Biomarker Identification and Screening
Biomarker identification and screening are crucial for successful drug discovery and development. During the early phases of drug discovery, biomarkers are needed that confirm the drug's action on the target, also known as pharmacodynamic biomarkers. Similarly, when entering the phase of phenotypic cellular screening, scientists need to understand which tumor cell lines will respond to the drug and why. The knowledge of predictive and pharmacodynamic biomarkers plays a crucial role in selecting suitable tumor models, data interpretation, and determining drug doses and treatment regimens. Identifying biomarkers will support the clinical phase of drug development with patient stratification and monitoring of drug effects in the patients.
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.
Data mining of large cell panel screens for cancer drug discovery.