Tumor stiffness is a critical factor influencing cancer progression, therapeutic resistance, and drug delivery. This study investigates the role of mechanical normalization in breast cancer therapy through the anti-fibrotic action of losartan, an angiotensin II type 1 receptor blocker. We developed a comprehensive multiphysics model integrating tumor cell proliferation, oxygen transport, interstitial fluid dynamics, and losartan pharmacokinetics/pharmacodynamics (PK/PD). Simulations demonstrate that losartan reduces tumor stiffness by up to 28%, enhances oxygenation by 8%, and increases tumor porosity by ~45%, thereby enhancing drug penetration and interstitial transport. Furthermore, tumor cell concentration decreased by 88%, reflecting the drug's dual anti-proliferative and pro-apoptotic effects. Spatial analyses revealed heterogeneity in stiffness reduction and drug response, emphasizing the importance of tumor geometry and perfusion. Our findings support the potential of losartan as a mechanotherapeutic adjuvant to enhance standard cancer treatments by remodeling the tumor microenvironment and overcoming mechanical barriers to therapy.
Copyright: © 2025 Dwairy et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.