Determinação da administração ótima de medicamentos de imunoterapia e quimioterapia no tratamento de câncer

Abstract

This study addresses the combination of immunotherapy and chemotherapy in cancer treatment, recognizing its promising effectiveness but highlighting the challenges of complex interactions between these therapeutic modalities. The central proposal is the use of computational models to simulate therapeutic responses, aiming for a systematic planning of individualized strategies. The main objective is to determine guidelines for the optimal administration of drugs, using an optimal control model that considers interactions in tumor dynamics, including cancer cells, the immune system, and therapeutic agents. The optimal control model is transformed into a multi-objective optimization problem with treatment constraints. This is achieved by introducing adjustable trade-offs, allowing personalized adaptations in drug administration to achieve an optimal balance between established objectives. Various optimization problems are addressed, considering two and three simultaneous objectives, such as minimizing the number of cancer cells and the density of effector cells at the final treatment time. The diverse combinations presented reflect the model’s flexibility in the face of multi-objective optimization, providing a range of approaches to meet specific medical needs. The analysis of Pareto optimal fronts in in-silico investigation offers an additional resource for decision-makers, enabling a more effective determination of the optimal administration of cytotoxic and immunotherapeutic agents.