Unravelling the in vivo traits of vasculogenic mimicry

Sep 23, 2026

Vasculogenic mimicry describes how cancer cells adopt endothelial-like properties, forming vessel-like channels that support tumour blood supply and contribute to resistance against anti-angiogenic therapies. Although molecular drivers have been studied in cell culture and biopsies, non-invasive detection and monitoring of these vascular networks in vivo remains unmet. The study presents a topology-first framework using label-free optical and photoacoustic imaging with graph-theory analysis to map spatiotemporal dynamics and evaluate response to Axitinib.

LanguageEnglish

CategoryHealthcare

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Pages17

Reading Time43 min

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Abstract

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Introduction

Theranostics 2026, Vol. 16, Issue 15 8633 Ivyspring International Publisher Theranostics 2026; 16(15): 8633-8649. doi: 10.7150/thno.140146 Research Paper Unravelling the in vivo traits of vasculogenic mimicry Mariam-Eleni Oraiopoulou1,2􀀍, Thierry L. Lefebvre1,2, Eleftheria Tzamali3, Thomas R. Else1,2, Ian G. Cannell1, Lorna C. Wright1,2, Ellie V. Bunce1,2, Cara Brodie1, Paul W. Sweeney1,2, Luca Porcu1, DominiqueLaurent Couturier4, Vangelis Sakkalis3, Gregory J. Hannon1†, Sarah E. Bohndiek1,2􀀍 1. Cancer Research UK Cambridge Institute (CRUK CI), University of Cambridge, Cambridge, UK. 2. Department of Physics, University of Cambridge, Cambridge, UK. 3. Institute of Computer Science, Foundation for Research and Technology – Hellas, Heraklion, Greece. 4. Medical Research Council Biostatistics Unit, University of Cambridge, Cambridge, UK. † Deceased during the revision of this manuscript. 􀀍 Corresponding authors: Mariam-Eleni Oraiopoulou ([Email: meo29@cam.ac.uk](Email: meo29@cam.ac.uk)) and Sarah E. Bohndiek (Email: [seb53@cam.ac.uk](seb53@cam.ac.uk)) . © The author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License ([https://creativecommons.org/licenses/by/4.0/](https://creativecommons.org/licenses/by/4.0/)). See [https://ivyspring.com/terms](https://ivyspring.com/terms) for full terms and conditions. Received: 2026.06.30; Accepted: 2026.07.07; Published: 2026.08.12 Abstract Vasculogenic mimicry describes the ability of cancer cells to acquire endothelial properties, forming vessel-like channels that facilitate tumour blood supply and can drive resistance to anti-angiogenic therapies. While the molecular drivers have been wellexplored in cell cultures and biopsies, vasculogenic mimicry remains a clinical blind spot as no methods exist to detect and monitor such vascular networks non-invasively in vivo. Methods: Here, we introduce a “topology-first” framework to define vasculogenic mimicry biomarkers and elucidate its spatiotemporal dynamics using label-free optical and photoacoustic imaging across scales. Using graph theory analysis, we decoded the unique vascular architecture of 4T1 and 4T1-T murine breast cancer models in response to anti-angiogenic treatment with Axitinib. Results: We found stable meshed networks in vitro and blood-containing circular structures in vivo serve as a key topological fingerprint for vasculogenic mimicry, conserved also in human breast cancer models. Crucially, these structures remained remodelling-resistant under anti-vascular therapy, signalling a potential functional mechanism of therapeutic escape. Conclusions: Our results provide the first evidence that vasculogenic mimicry features can be mapped non-invasively through topology, offering a potential future companion diagnostic and method to guide the development of next-generation, multi-target anti-vascular therapeutics. Keywords: cancer; vasculogenic mimicry; tumour vascular network; imaging biomarkers; anti-angiogenic therapy Introduction Vascularisation in a solid tumour mass proceeds via a range of mechanisms, from vessel co-option and sprouting or intussusceptive angiogenesis, to vasculogenic mimicry (VM) [1] . Vasculogenic mimics are shunt hypoperfused blood vessels with a lamininrich basement membrane that contribute to cancer microcirculation, but, unlike other neo-vascularisation mechanisms, are not composed of endothelial cells [2- 4] . VM vessels exist amongst the co-opted host and angiogenic vessels [2], but can also hijack adjacent endothelial cells to create vessel mosaics [5] . While the molecular drivers of VM have been explored, its presence remains a critical clinical “blind spot”. Despite VM being implicated in the failure of anti- angiogenic therapies, we are not currently able to identify patients whose tumours exhibit VM in vivo and thus may be refractory to anti-angiogenic treatment. A range of conditions, from perva

FAQs

What is vasculogenic mimicry and why is it clinically important?

Vasculogenic mimicry is when cancer cells acquire endothelial-like properties to form vessel-like channels that facilitate tumour blood supply and can drive resistance to anti-angiogenic therapies. It remains a clinical blind spot because there are no established non-invasive ways to detect and monitor the vascular networks in vivo.

What approach does the study introduce to detect vasculogenic mimicry?

The study introduces a “topology-first” framework to define vasculogenic mimicry biomarkers and uses graph theory analysis. It combines label-free optical and photoacoustic imaging to elucidate spatiotemporal dynamics across scales.

What topological signatures were found in vitro and in vivo?

Stable meshed networks in vitro and blood-containing circular structures in vivo were identified as key topological fingerprints of vasculogenic mimicry. These features were conserved in human breast cancer model settings discussed in the results.

Sep 23, 2026

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