Cell death and survival due to cytotoxic exposure modelled as a two-state Ising system

Abstract

Cancer chemotherapy agents are assessed for their therapeutic utility primarily by their ability to cause apoptosis of cancer cells and their potency is given by an IC50 value. Chemotherapy uses both target-specific and systemic-action drugs and drug combinations to treat cancer. It is important to judiciously choose a drug type, its dosage and schedule for optimized drug selection and administration. Consequently, the precise mathematical formulation of cancer cells' response to chemotherapy may assist in the selection process. In this paper, we propose a mathematical description of the cancer cell response to chemotherapeutic agent exposure based on a time-tested physical model of two-state multiple-component systems near criticality. We describe the Ising model methodology and apply it to a diverse panel of cytotoxic drugs administered against numerous cancer cell lines in a dose–response manner. The analysed dataset was generated by the Netherlands Translational Research Center B.V. (Oncolines). This approach allows for an accurate and consistent analysis of cytotoxic agents' effects on cancer cell lines and reveals the presence or absence of the bystander effect through the interaction constant. By calculating the susceptibility function, we see the value of IC50 coinciding with the peak of this measure of the system's sensitivity to external perturbations.