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3D Cultures and Organoids in Cancer Research

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Molecular Cancer Biology".

Deadline for manuscript submissions: 28 February 2026 | Viewed by 5725

Special Issue Editors


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Guest Editor
International Laboratory EPIGEN, Consejo de Ciencia y Tecnología del Estado de Puebla (CONCYTEP), Instituto de Ciencias, Ecocampus, Benemérita Universidad Autónoma de Puebla (BUAP), Puebla 72570, Mexico
Interests: the mechanisms of epigenetic regulation in cancer subtypes; lung diseases; neurodegenerative diseases and diseases associated with environmental pollution

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Guest Editor
Posgrado en Ciencias Genómicas, Universidad Autónoma de la Ciudad de México, CDMX 03100, Mexico
Interests: microRNAs; lncRNAs; circRNAs; proteins; cancers; novel therapeutic targets; tumorigenesis; nutrigenomics; 3D cultures
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Special Issue Information

Dear Colleagues,

Three-dimensional (3D) cell cultures more accurately mimic the spatial architecture of tumors; therefore, they represent an innovative approach to discovering the complex biology of cancer. Moreover, recent advances in organoid technologies have enabled the construction of 3D models of patient-derived tumors in vitro. These models can better mimic tumor architecture, tumor microenvironment, and gene expression portraits. Three-dimensional cell cultures can better recapitulate the molecular features of in vivo tumor tissues, such as cell heterogeneity, oxygen and nutrient gradients, hypoxia grades, and the activation of oncogenic signaling pathways. Therefore, implementing reliable in vitro cancer 3D cultures containing cellular components of the stroma and extracellular matrix may provide information about its impact on the genetic programs leading to breast cancer development and progression. These characteristics significantly influence the reprogramming of non-coding RNAs’ and mRNAs' epigenetic and gene expression patterns. Three-dimensional cultures and organoids are a powerful tool in precision medicine and discovering new therapeutic targets. The advantages of 3D cultures include the ability to identify key genes and proteins that could be translated into developing novel therapeutic strategies.

This Special Issue aims to collate original research and review articles that cover recent advances in understanding the role of innovative 3D cell cultures and organoid models and their applications in elucidating the molecular mechanisms of cancer development and progression, drug screening, and personalized medicine.

This collection welcomes original research on the promises and challenges of 3D culture. Original research articles and reviews are welcome. Research areas may include (but are not limited to) the following:

  • 3D cell cultures.
  • Organotypic 3D cultures.
  • 3D spheroids systems.
  • Induced pluripotent stem (iPS) cell-derived organoids.
  • Genome-wide profiling of non-coding RNAs in 3D cultures.
  • 3D cell cultures and organoid models for cancer stroma cells and the tumor microenvironment.

We look forward to receiving your contributions.

Dr. Karla Rubio
Prof. Dr. César López-Camarillo
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 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. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). 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 cell cultures
  • organotypic 3D cultures
  • 3D spheroids models
  • induced pluripotent stem (iPS)
  • organoids
  • tumoroids

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Published Papers (2 papers)

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Review

42 pages, 2533 KB  
Review
Epigenetic and Transcriptional Reprogramming in 3D Culture Models in Breast Cancer
by Laura Cecilia Flores-García, Karla Rubio, Eloisa Ibarra-Sierra, Macrina B. Silva-Cázares, Carlos Palma-Flores and César López-Camarillo
Cancers 2025, 17(23), 3830; https://doi.org/10.3390/cancers17233830 - 29 Nov 2025
Viewed by 168
Abstract
Breast cancer remains the leading cause of cancer-related death in women worldwide. This disease is characterized by its molecular and phenotypic heterogeneity, which hinders the development of effective therapies. While two-dimensional (2D) monolayer cell cultures are widely used, they are insufficient to reproduce [...] Read more.
Breast cancer remains the leading cause of cancer-related death in women worldwide. This disease is characterized by its molecular and phenotypic heterogeneity, which hinders the development of effective therapies. While two-dimensional (2D) monolayer cell cultures are widely used, they are insufficient to reproduce the characteristics of the tumor microenvironment, thus limiting our understanding of cancer biology. In this context, three-dimensional (3D) models have emerged as representative tools that more accurately reproduce tissue architecture, cell signaling, and nutrients and oxygen gradients. These cellular models offer greater similarity to primary tissues, improving the study of relevant biological processes. Although 3D cultures provide numerous advantages in cancer research, there is no unified model that standardizes the matrix type and parameters such as gelation time or porosity, hindering the reproducibility and interpretability of the data. This review integrates evidence from various studies to evaluate the effect of epigenetic variations generated by 3D culture methods, which are regulated by mechanotransduction and, consequently, by signaling pathways such as integrin/FAK-ILK/Rho-YAP derived from interactions of cells with extracellular matrix-enriched scaffolds. This affects processes such as DNA methylation, histone coding, and the regulation of non-coding RNAs such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) in different molecular subtypes of breast cancer. Overall, the evidence highlights that 3D culture methods are not equivalent but rather generate distinct epigenetic signatures at the non-coding RNA level that influence the proliferation, differentiation, therapeutic resistance, and metastatic potential of tumor cells. Furthermore, the evidence suggests that histone coding patterns, primarily through the reduction of acetylation marks, are conserved regardless of the type of 3D culture. In summary, the study highlights that the microarchitectural and compositional characteristics of 3D scaffolds are key determinants of epigenetic plasticity. Full article
(This article belongs to the Special Issue 3D Cultures and Organoids in Cancer Research)
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21 pages, 2024 KB  
Review
Spatial Transcriptomics in Lung Cancer and Pulmonary Diseases: A Comprehensive Review
by Da Hyun Kang, Yoonjoo Kim, Ji Hyeon Lee, Hyeong Seok Kang and Chaeuk Chung
Cancers 2025, 17(12), 1912; https://doi.org/10.3390/cancers17121912 - 9 Jun 2025
Cited by 4 | Viewed by 5136
Abstract
Recent advancements in spatial transcriptomics (ST) have revolutionized our understanding of the lung’s cellular organization and pathological alterations. By preserving the spatial distribution of gene expression, ST reveals localized immune niches, stromal–epithelial interactions, and disease-associated transcriptional “hotspots” that cannot be captured by conventional [...] Read more.
Recent advancements in spatial transcriptomics (ST) have revolutionized our understanding of the lung’s cellular organization and pathological alterations. By preserving the spatial distribution of gene expression, ST reveals localized immune niches, stromal–epithelial interactions, and disease-associated transcriptional “hotspots” that cannot be captured by conventional sequencing methods alone. In lung cancer, ST-based investigations have delineated distinct tumor microenvironments between tumor cores and invasive fronts, revealing prognostically significant gene signatures and identifying subpopulations with differential responses to immunotherapy and chemotherapy. Similarly, in chronic obstructive pulmonary disease, asthma, and idiopathic pulmonary fibrosis, ST has mapped the ecosystem, including immune cells, inflammatory mediators, and fibroblast subtypes, of discrete regions within diseased lung tissue, offering mechanistic insights into disease progression and tissue remodeling. In addition, a more recent ST study provides spatial information for where drugs act within tissues. This review highlights the emerging role of spatial transcriptomics in respiratory research, demonstrating its potential to refine disease classification, elucidate mechanisms of therapeutic resistance, and inform spatially guided personalized interventions in respiratory diseases. Full article
(This article belongs to the Special Issue 3D Cultures and Organoids in Cancer Research)
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