Spatial organization of mediated-macrophage chemoprotective niches in solid tumors: A mathematical analysis
Year: 2025
Type: article
Abstract: Acquired resistance is one of the major causes of failure of standard therapies in cancer patients. Chemotherapeutic agents are still widely used and the understanding of the mechanisms leading to secondary resistance to these molecules are still puzzling. Recently, the role of the tumor immune microenvironment has been recognized. Among the cells potentially involved, macrophages seem to be the perfect culprits. In a previous work, we have shown that hypoxic macrophages are able to provide strong protection against 5-fluorouracil, a first-line chemotherapeutic agent in digestive cancers. In the present work, we use mathematical modeling to explore the spatiotemporal aspects of the treatment-induced organization of the tumor environment. Based on analytical and numerical analysis, we propose that macrophage-driven protection against chemotherapy under treatment does not rely solely on biochemical degradation, but is enhanced by the emergence of spatially structured chemotherapeutic protective niches. This work paves the way for the development of new therapeutic strategies that rely on targeting the spatial organization of tumors as a way to control treatment resistance.
DOI: 10.1051/mmnp/2025012
Authors: William Dangelser, Angelique Stephanou, Arnaud Millet
Language: English
Subfield: Modeling and Simulation
Field: Mathematics
Domain: Physical Sciences
Open Access status: hybrid
Estimated APC paid:
OpenAlex ID: W4409008248