ArticlePloS one2025
Losartan as a mechanotherapeutic adjuvant: Remodeling the breast tumor microenvironment to improve treatment efficacy.
Article in PloS one, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- Hippo pathway at the crossroads of stemness and therapeutic resistance in breast cancer.Molecular oncology · 2026Review
- A multiphysics computational model of focused ultrasound-enhanced drug delivery using temperature-sensitive liposomes.Biomechanics and modeling in mechanobiology · 2026Article
- The mechano-immunological landscape in the tumor microenvironment: From mechanical sensing to a new therapeutic paradigm.Materials today. Bio · 2026Review
- Normalizing the Tumor Microenvironment: A New Frontier in Ovarian Cancer Therapy.International journal of molecular sciences · 2026Review
- Advances in Drug Delivery Systems for Breast Cancer: From Microenvironment Barriers and Smart Carriers to Clinical Translation Strategies.Drug design, development and therapy · 2026Review
- Current Status of Research on Losartan in Tumour Therapy.Journal of cellular and molecular medicine · 2026Review
- The mechano-immunological barrier in fibrosis-associated lung cancer: targeting matrix stiffness and the Piezo1 axis for microenvironment normalization.Frontiers in pharmacology · 2026Review
Corrections and comments
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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.
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