Evaluating the influence of mechanical stress on anticancer treatments through a multiphase porous media model

JOURNAL OF THEORETICAL BIOLOGY

卷:421

Article

Mascheroni, Pietro¹  Boso, Daniela¹  Preziosi, Luigi²  Schrefler, Bernhard A.^3,4 

[1] Univ Padua, Dipartimento Ingn Civile Edile & Ambientale, Via Marzolo 9, I-35131 Padua, Italy

[2] Politecn Torino, Dipartimento Sci Matemat, Corso Duca Abruzzi 24, I-10124 Turin, Italy

[3] Tech Univ Munich, Inst Adv Study, Lichtenbergstr 2, D-85748 Garching, Germany

[4] Houston Methodist Res Inst, 6670 Bertner Ave, Houston, TX 77030 USA

关键词: Cancer;    Chemotherapy;    Tumor spheroids;    Mathematical model;    Mechanical compression;   

DOI  :  10.1016/j.jtbi.2017.03.027

来源: Elsevier

【 摘 要 】

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. (C) 2017 Elsevier Ltd. All rights reserved.

【 授权许可】

Free