Biphasic Mathematical Model of Cell-Drug Interaction That Separates Target-Specific and Off-Target Inhibition and Suggests Potent Targeted Drug Combinations for Multi-Driver Colorectal Cancer Cells.

ABSTRACT: Quantifying the response of cancer cells to a drug, and understanding the mechanistic basis of the response, are the cornerstones for anti-cancer drug discovery. Classical single target-based IC50 measurements are inadequate at describing cancer cell responses to targeted drugs. In this study, based on an analysis of targeted inhibition of colorectal cancer cell lines, we develop a new biphasic mathematical model that accurately describes the cell-drug response. The model describes the drug response using three kinetic parameters: ratio of target-specific inhibition, F1, potency of target-specific inhibition, Kd1, and potency of off-target toxicity, Kd2. Determination of these kinetic parameters also provides a mechanistic basis for predicting effective combination targeted therapy for mul

SUBMITTER: Shen J 

PROVIDER: S-EPMC7072552 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature