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Recent Advances in 3D Tumor Models for Cancer Research
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Recent Advances in 3D Tumor Models for Cancer Research

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: 20 December 2025 | Viewed by 4977

Special Issue Editors

Dr. Simona Campora

E-Mail Website
Guest Editor
Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, Viale delle Scienze, Ed. 16, 90128 Palermo, Italy
Interests: regenerative medicine; tissue engineering; nanoparticles; tumor therapy; cell isolation; primary cell culture
Special Issues, Collections and Topics in MDPI journals
Dr. Francesco Lopresti

E-Mail Website
Guest Editor
Department of Engineering, University of Palermo, Viale delle Scienze, Ed. 6, 90128 Palermo, Italy
Interests: scaffolds for regenerative medicine; electrospinning; thermally induced phase separation; hydrogels; bioprinting; organ-on-chip; bionanocomposites
Special Issues, Collections and Topics in MDPI journals
Dr. Alessandra Lo Cicero

E-Mail Website
Guest Editor
Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, Viale delle Scienze, Ed. 16, 90128 Palermo, Italy
Interests: extracellular vesicles; exosomes; cancer biochemistry; tumor microenvironment; drug delivery
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Three-dimensional (3D) cancer models have emerged as a promising approach to bridging the gap between traditional 2D systems and in vivo studies. These models, which include spheroids, assembloids, organoids, scaffolds, and organ-on-chip systems, more accurately mimic physiological conditions by incorporating not only cancer cells but also key components of the tumor microenvironment, such as cancer-associated fibroblasts (CAFs), immune and endothelial cells, components of the extracellular matrix, and other physiochemical stimuli. These advanced systems enable a deeper investigation of the physiological and biochemical pathways underlying tumor development and progression, serving as optimal platforms for drug screening and evaluation. This multidisciplinary field spans areas like biochemistry, cancer research, bioengineering, medicine, molecular biology, and pharmacology.

As guest editors, we warmly invite academic and industry researchers to submit high-quality reviews or original articles. Contributions should address key challenges and advancements, emphasizing the latest developments and cutting-edge strategies in 3D cancer modeling.

We look forward to your contributions.

Dr. Simona Campora
Dr. Francesco Lopresti
Dr. Alessandra Lo Cicero
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • 3D systems
  • cancer research
  • spheroids
  • organoids
  • organ-on-chip
  • scaffolds
  • tissue engineering
  • biomedical technologies
  • tumor microenvironment

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Published Papers (3 papers)

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Research

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18 pages, 2566 KB  
Article
Feasibility of Patient-Derived 3D Gastrointestinal Stromal Tumour Models as Alternatives for In Vivo Mouse Models
by Dina Mönch, Julia Thiel, Meng Dong, Annika Maaß, Eileen Wegner, Anna Binner, Annette M. Staiger, Katrin S. Kurz, German Ott, Philipp Renner, Tobias Leibold, Christian Schmees, Thomas E. Mürdter, Matthias Schwab, Marc-H. Dahlke and Jana Koch
Int. J. Mol. Sci. 2025, 26(23), 11456; https://doi.org/10.3390/ijms262311456 - 26 Nov 2025
Viewed by 187
Abstract
Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal tumours of the gastrointestinal tract and a key example for targeted therapy with tyrosine kinase inhibitors (TKIs), which have significantly improved survival rates. However, no effective treatments exist for TKI-resistant or mutation-negative tumours. Until [...] Read more.
Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal tumours of the gastrointestinal tract and a key example for targeted therapy with tyrosine kinase inhibitors (TKIs), which have significantly improved survival rates. However, no effective treatments exist for TKI-resistant or mutation-negative tumours. Until now, research on the effects of TKIs has mainly used 2D cultures or mouse models, lacking patient-specific 3D GIST models. We investigated various 3D GIST models, including spheroids, organoids, patient-derived microtumours (PDMs), and precision-cut tumour slices (PCTSs), to assess their feasibility as alternatives for 2D cell culture or in vivo mouse models. Moreover, 2D monolayer and 3D spheroid GIST cell lines showed mutation-dependent responses to TKI treatment, but differences between 2D and 3D cultures were minimal. Thus, patient-derived 3D models, incorporating tumour microenvironment cells, were developed for more accurate in vivo representation. PDMs and PCTSs were successfully isolated from primary tumours and cultivated for up to two weeks. Three-dimensional models were immunohistochemically characterised, and the response to TKI therapies was tested and compared with expected clinical outcomes. In addition to already established 2D cell cultures and mouse models, PDMs and PCTSs are novel patient-derived 3D models that can be used to study tumour cell interactions within the microenvironment. Moreover, they could be used to investigate TKI resistance, and novel treatment options such as immunotherapies and combination therapies. Full article
(This article belongs to the Special Issue Recent Advances in 3D Tumor Models for Cancer Research)
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Review

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23 pages, 1912 KB  
Review
Utility of Multicellular Spheroids for Investigating Mechanisms of Chemoresistance in Triple-Negative Breast Cancer
by Keith N. Ncube, Iman van den Bout, Clarissa Willers, Chrisna Gouws and Werner Cordier
Int. J. Mol. Sci. 2025, 26(15), 7503; https://doi.org/10.3390/ijms26157503 - 3 Aug 2025
Cited by 2 | Viewed by 1672
Abstract
Chemoresistance is a major challenge in the treatment of triple-negative breast cancer (TNBC). Multicellular spheroids are an attractive platform for investigating chemoresistance in TNBC, as they replicate the cues of the tumour microenvironment in vivo. We conducted a comprehensive literature search to summarise [...] Read more.
Chemoresistance is a major challenge in the treatment of triple-negative breast cancer (TNBC). Multicellular spheroids are an attractive platform for investigating chemoresistance in TNBC, as they replicate the cues of the tumour microenvironment in vivo. We conducted a comprehensive literature search to summarise the multifactorial and interlinked mechanisms driving chemoresistance in TNBC spheroids. These mechanisms include spatial heterogeneity, hypoxia, extracellular matrix remodelling, tumour–stroma crosstalk, drug efflux, apoptotic resistance, and cancer stem cell signalling. Strategies for overcoming chemoresistance in TNBC spheroids include nanocarrier systems to overcome spatial diffusion limitations, pathway inhibition, and targeting tumour–microenvironment interactions. Despite their advantages, some spheroid models face challenges such as low reproducibility, a lack of heterogeneity, variability in size and shape, limited vascularisation, and constraints in long-term culture. Advanced culturing platforms such as clinostat bioreactors allow for extended culture periods, enabling mature spheroid drug testing. Furthermore, advanced analytical techniques provide spatially resolved spheroid data. These multifactorial and interlinked mechanisms reflect the tumour microenvironment in vivo that spheroids recapitulate, rendering them valuable models for studying chemoresistance. The incorporation of stromal components and advanced analytical workflows will enhance the utility and translational relevance of spheroids as reliable preclinical models for drug discovery in TNBC. Full article
(This article belongs to the Special Issue Recent Advances in 3D Tumor Models for Cancer Research)
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27 pages, 1804 KB  
Review
The 3D Language of Cancer: Communication via Extracellular Vesicles from Tumor Spheroids and Organoids
by Simona Campora and Alessandra Lo Cicero
Int. J. Mol. Sci. 2025, 26(15), 7104; https://doi.org/10.3390/ijms26157104 - 23 Jul 2025
Cited by 1 | Viewed by 2628
Abstract
Extracellular vesicles (EVs) have emerged as key mediators of intercellular communication, gaining recognition as tumor biomarkers and promising therapeutic targets. As the study of EVs advances, it has become increasingly clear that the cellular context in which they are produced significantly influences their [...] Read more.
Extracellular vesicles (EVs) have emerged as key mediators of intercellular communication, gaining recognition as tumor biomarkers and promising therapeutic targets. As the study of EVs advances, it has become increasingly clear that the cellular context in which they are produced significantly influences their composition and function. Traditional two-dimensional in vitro models are being progressively replaced by more advanced three-dimensional systems, such as tumor spheroids and organoids. These 3D models are particularly valuable in cancer research, providing a more accurate representation of the complex cellular and molecular heterogeneity that characterizes tumors, better mimicking the in vivo microenvironment compared to standard monolayer cultures. This review explores the role of EVs derived from tumor spheroids and organoids in key oncogenic processes, including tumor growth, metastasis, and interactions within the tumor microenvironment. We highlight how EVs contribute to the spread of cancer cells, affecting surrounding tissues, and promote immune evasion, which poses significant challenges in cancer therapy. Full article
(This article belongs to the Special Issue Recent Advances in 3D Tumor Models for Cancer Research)
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