Absence of convection in solid tumors caused by raised interstitial fluid pressure severely limits success of chemotherapy-a numerical study in cancers
Open accessAbstract
In comparison with lymphomas and leukemias, chemotherapy of solid neoplasms, i.e., cancer, has much more limited success in curing the patient. This lack of efficacy of chemotherapy has been attributed to increased interstitial fluid pressure within cancers, which obstructs convection and only permits diffusion of oxygen and nutrients about 100 μm from blood vessels. As diffusion is limited to this distance, hypoxic and necrotic fractions within the tumor are observed beyond this region. The comparably small number of cancer cells that can be targeted with drugs inevitably leads to an ineffective treatment response. This study presents an analysis of the influence of interstitial fluid pressure on the chemotherapeutic effect in an HT29 human colon cancer xenograft mouse tumor model. To investigate the limited distribution of drugs into primary tumor and metastases, we developed a mathematical model describing tumor growth dynamics of oxygenated, hypoxic, and necrotic fractions, combined with a pharmacokinetic-pharmacodynamic model describing the behavior and effectivity of the chemotherapeutic agent. According to the numerical simulations, the age of the tumor at treatment was the decisive factor in the reduction in size of the primary tumor. This effect is mediated by the rapid decrease in the percentage of oxygenated cells within the tumor, which reduces the fraction of cells that can be affected by the drug. As in the primary tumor, interstitial fluid pressure builds up in metastases when they reach a specific size, leading to the formation of tumor fractions. This behavior is absent if the metastasis enters a dormant phase before the threshold for the development of interstitial fluid pressure has been reached. The small size of these metastases maximizes therapeutic success since they consist only of oxygenated cells, and the drug therefore affects all the cells.
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Drug distribution in tumors becomes reliant on diffusion alone, which is inefficient in the context of dense ECM and spatial heterogeneity characteristic of solid tumors.
“Consequently, drug distribution becomes reliant on diffusion alone, which is inefficient in the context of the dense ECM and spatial heterogeneity characteristic of solid tumors [99,154,155,156].”
From Modeling Tumor Microenvironment Complexity In Vitro: Spheroids as Physiologically Relevant Tumor Models and Strategies for Their Analysis (2025) · cites this paper as [156]
The Introduction (page unavailable) says convection is absent in cancers, leaving transport more or less limited to diffusion, and reports that anticancer drugs penetrate only about 100 µm from blood vessels. The Conclusions (page unavailable) link this limited distribution to reduced chemotherapy effectiveness. The paper does not attribute the limitation to dense ECM; its explanation centers on raised interstitial fluid pressure, though it does describe differences in drug access across tumor regions. (LLM, conf=0.86)
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Shah, S., & D’Souza, G. G. M. (2025) · Cells · doi:10.3390/cells14100732 · Cited by 66 · see citing works
- Authors
- Hoffmann, B., 1 Competence Center Bioinformatics, I. F. A. C. S., Schumacher, U., Wedemann, G., & 2 Institute for Anatomy and Experimental Morphology, U. C. C.
- Affiliations
- University of Applied Sciences Stralsund (DE)
- University Medical Center Hamburg-Eppendorf (DE)
- Corresponding author
- Wedemann, Gero
- Venue
- Mathematical Biosciences and Engineering
- Published
- 2020
- Volume
- 17
- Issue
- 5
- Pages
- 6128-6148
- ISSN
- 1547-1063 (ISSN-L)
- 1551-0018
- OpenAlex
- W3085783522
- Cited by
- 9
- References
- 0
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 2 · 2023: 1 · 2022: 1
- FWCI
- 0.08
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc-sa
- Locations
- Mathematical Biosciences & Engineering (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Physical Sciences › Mathematics › Modeling and Simulation › Mathematical Biology Tumor Growth
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Keywords
- interstitial fluid pressure, solid tumors, chemotherapy efficacy, tumor hypoxia, tumor necrosis, drug diffusion, tumor growth kinetics, pharmacokinetic-pharmacodynamic modeling, colon cancer xenografts, HT-29 cells, tumor age
- MeSH terms
- Animals, Antineoplastic Agents, Humans, Models, Biological, Neoplasms, Convection, Extracellular Fluid, Mice
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