Exposure-response modeling improves selection of radiation and radiosensitizer combinations

• DOI: 10.1007/s10928-021-09784-7
• Publication Date: 2021-10-09T05:16:34Z
• Authors: Tim Cardilin; Joachim Almquist; Mats Jirstrand; Astrid Zimmermann; Floriane Lignet; Samer El Bawab; Johan Gabrielsson
• Keywords: Radiosensitizer

A central question in drug discovery is how to select candidates from a large number of available compounds. This analysis presents model-based approach for comparing and ranking combinations radiation radiosensitizers. The quantitative based on the previously-derived Tumor Static Exposure (TSE) concept. Combinations radiosensitizers are evaluated their ability induce tumor regression relative toxicity other potential costs. presented form case study where objective find most promising candidate out three radiosensitizing agents. Data xenograft described using nonlinear mixed-effects modeling previously-published model First, chosen under assumption that all compounds equally toxic. impact compound selection then illustrated by assuming one more toxic than others, leading different choice candidate.