title: Evaluating the influence of mechanical stress on anticancer treatments through a multiphase porous media model.
abstract: Drug resistance is one of the leading causes of poor therapy outcomes in cancer. As several chemotherapeutics are designed to target rapidly dividing cells, the presence of a low-proliferating cell population contributes significantly to treatment resistance. Interestingly, recent studies have shown that compressive stresses acting on tumor spheroids are able to hinder cell proliferation, through a mechanism of growth inhibition. However, studies analyzing the influence of mechanical compression on therapeutic treatment efficacy have still to be performed. In this work, we start from an existing mathematical model for avascular tumors, including the description of mechanical compression. We introduce governing equations for transport and uptake of a chemotherapeutic agent, acting on cell proliferation. Then, model equations are adapted for tumor spheroids and the combined effect of compressive stresses and drug action is investigated. Interestingly, we find that the variation in tumor spheroid volume, due to the presence of a drug targeting cell proliferation, considerably depends on the compressive stress level of the cell aggregate. Our results suggest that mechanical compression of tumors may compromise the efficacy of chemotherapeutic agents. In particular, a drug dose that is effective in reducing tumor volume for stress-free conditions may not perform equally well in a mechanically compressed environment.
authors.affiliation: Dipartimento di Ingegneria Civile, Edile ed Ambientale, Università di Padova, Via Marzolo 9, 35131 Padova, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Mascheroni
authors.affiliation: Dipartimento di Ingegneria Civile, Edile ed Ambientale, Università di Padova, Via Marzolo 9, 35131 Padova, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Boso
authors.affiliation: Dipartimento di Scienze Matematiche, Politecnico di Torino, Corso Duca degli Abruzzi 24, 10124 Torino, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Preziosi
authors.affiliation: Institute for Advanced Study, Technische Universität München, Lichtenbergstraße 2, 85748 Garching bei München, Germany and Houston Methodist Research Institute, 6670 Bertner Ave, Houston, TX 77030, USA. Electronic address: bernhard.schrefler@dicea.unipd.it.
authors.forename: Bernhard A
authors.initials: BA
authors.lastname: Schrefler
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D045744:Cell Line, Tumor; D019245:Compressive Strength; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008954:Models, Biological; D008962:Models, Theoretical; D016062:Porosity; D018874:Spheroids, Cellular / Q000378:metabolism; D013314:Stress, Mechanical
chemical_list: D000970:Antineoplastic Agents
keywords: Cancer; Chemotherapy; Mathematical model; Mechanical compression; Tumor spheroids