Tumor interstitial fluid pressure as an early-response marker for anticancer therapeutics
Open accessAbstract
Solid tumors have a raised interstitial fluid pressure (IFP) due to high vessel permeability, low lymphatic drainage, poor perfusion, and high cell density around the blood vessels. To investigate tumor IFP as an early-response biomarker, we have tested the effect of seven anticancer chemotherapeutics including cytotoxics and targeted cytostatics in 13 experimental tumor models. IFP was recorded with the wick-in-needle method. Models were either ectopic or orthotopic and included mouse and rat syngeneic as well as human xenografts in nude mice. The mean basal IFP was between 4.4 and 15.2mm Hg; IFP was lowest in human tumor xenografts and highest in rat syngeneic models. Where measured, basal IFP correlated positively with relative tumor blood volume (rTBV) determined by dynamic contrast-enhanced magnetic resonance imaging. Most chemotherapeutics sooner (2 or 3 days) or later (6 or 7 days) lowered tumor IFP significantly, and the cytotoxic patupilone caused the greatest decrease in IFP. In rat mammary orthotopic BN472 tumors, significant drug-induced decreases in IFP and rTBV correlated positively with each other for both patupilone and the cytostatic vatalanib. In the two orthotopic models studied, early decreases in IFP were significantly (P < or = .005) correlated with late changes in tumor volume. Thus, drug-induced decreases in tumor IFP are an early marker of response to therapy, which could aid clinical development.
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Increased ECM stiffness and compactness restrict intercellular space, further compromising the efficacy of therapeutic delivery.
“Additionally, increased ECM stiffness and compactness restrict intercellular space, further compromising the efficacy of therapeutic delivery [89,90].”
From Modeling Tumor Microenvironment Complexity In Vitro: Spheroids as Physiologically Relevant Tumor Models and Strategies for Their Analysis (2025) · cites this paper as [90]
The Introduction (page not provided) says that compressed blood vessels and inadequate lymphatic drainage reduce fluid movement through the tumor interstitium. The Discussion (page not provided) mentions high tumor-cell density, but neither passage addresses ECM stiffness or compactness restricting intercellular space and impairing therapeutic delivery. Searches for those terms and for drug penetration found no supporting passage in our copy. (LLM, conf=0.72)
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“Additionally, increased ECM stiffness and compactness restrict intercellular space, further compromising the efficacy of therapeutic delivery [89,90].”
- Authors
- Ferretti, S., Allegrini, P. R., Becquet, M. M., & McSheehy, P. M. J.
- Affiliations
- Novartis (Switzerland) (CH)
- Venue
- Neoplasia
- Publisher
- Elsevier BV
- Published
- 2009-09
- Volume
- 11
- Issue
- 9
- Pages
- 874-881
- ISSN
- 1476-5586 (ISSN-L)
- PMC
- PMC2735799
- OpenAlex
- W1604408587
- Cited by
- 106
- References
- 0
- Citations by year
- 2026: 7 · 2025: 3 · 2024: 8 · 2023: 12 · 2022: 6 · 2021: 5 · 2020: 4 · 2019: 10 · 2018: 4 · 2017: 4 · 2016: 5 · 2015: 4 · 2014: 6 · 2013: 6 · 2012: 6
- FWCI
- 7.33
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Neoplasia (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Topics
- Physical Sciences › Mathematics › Modeling and Simulation › Mathematical Biology Tumor Growth
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Health Sciences › Medicine › Oncology › Lymphatic System and Diseases
- Keywords
- tumor interstitial fluid pressure, early response biomarkers, cancer chemotherapy, patupilone, vatalanib, tumor blood volume, tumor perfusion, tumor microenvironment, orthotopic tumor model, xenografts, syngeneic tumors, drug response prediction
- MeSH terms
- Animals, Antineoplastic Agents, Contrast Media, Female, Humans, Magnetic Resonance Imaging, Mice, Inbred BALB C, Mice, Inbred C3H, Mice, Inbred C57BL, Mice, Nude, Neoplasms, Rats, Inbred BN, Biomarkers, Tumor, Xenograft Model Antitumor Assays, Extracellular Fluid, Mice, Rats
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