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Breast Cancer Microenvironment: Molecular Mechanisms and Therapeutic Targeting

A Special Issue of Cancers (ISSN 2072-6694) belonging to the section "Tumor Microenvironment".

Deadline for manuscript submissions: 30 September 2026 | Viewed by 1016

Editor


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Guest Editor
Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Chaoyang, Beijing 100021, China
Interests: tumor microenvironment; breast cancer research; single cell/space transcriptome sequencing; machine learning

Special Issue Information

Dear Colleagues,

The breast cancer microenvironment (TME) plays a pivotal role in tumor progression, metastasis, and therapy resistance, yet its complex molecular crosstalk remains incompletely understood. This Special Issue seeks to highlight cutting-edge research elucidating the interplay between cancer cells and stromal components—fibroblasts, immune cells, endothelial cells, and extracellular matrix—within the breast TME. We welcome studies uncovering novel molecular drivers (e.g., ligand-receptor networks, epigenetic regulators, signaling pathways), mechanisms of microenvironment remodeling (e.g., ECM stiffness, metabolic reprogramming), and innovative therapeutic strategies targeting TME vulnerabilities (e.g., stromal-targeted therapies, immunotherapy combinations). Topics include, but are not limited to, the following:

  • Fibroblast–cancer cell interactions in metastasis;
  • Immune evasion and TME immunomodulation;
  • Metabolic coupling between cancer and stromal cells;
  • Biomarkers derived from TME features for prognosis/therapy guidance;
  • Preclinical and clinical advances in TME-targeted interventions.

By integrating mechanistic insights with translational perspectives, this issue aims to accelerate progress toward precision therapies for breast cancer.

Dr. Yi Fang
Guest Editor

Manuscript Submission Information

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Keywords

  • breast cancer
  • tumor microenvironment
  • biomarkers
  • therapeutic targeting
  • tumor-stromal interactions
  • precision oncology

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Published Papers (2 papers)

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Research

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24 pages, 20825 KB  
Article
Inhibition of IGF1R in Early MMTV-Wnt1 Mammary Tumors: A Transcriptomic Analysis
by Joseph J. Bulatowicz, Alexander Lemenze, Elvan Dogan, Christopher A. Galifi, Krystopher Maingrette, Quan Shang and Teresa L. Wood
Cancers 2026, 18(11), 1749; https://doi.org/10.3390/cancers18111749 - 27 May 2026
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Abstract
Background: The insulin-like growth factor 1 receptor (IGF1R) is a receptor tyrosine kinase whose both overexpression and underexpression have been implicated in the initiation and progression of breast tumorigenesis. The mechanism through which underexpression of the receptor contributes to a more aggressive [...] Read more.
Background: The insulin-like growth factor 1 receptor (IGF1R) is a receptor tyrosine kinase whose both overexpression and underexpression have been implicated in the initiation and progression of breast tumorigenesis. The mechanism through which underexpression of the receptor contributes to a more aggressive phenotype is currently less understood. Methods: Through the expression of a dominant-negative IGF1R, we studied the phenotypic effects of receptor inhibition on early MMTV-Wnt1 mouse mammary tumors. Utilizing histopathological techniques and single-cell RNA-sequencing, we explored cellular heterogeneity and transcriptional alterations that occur as a result of IGF1R inhibition. Results: Examination of primary tumors failed to reveal obvious differences in tissue architecture or expression of differentiation markers with IGF1R inhibition. Both cohorts of tumors produced metastatic lesions in the lung. Single-cell RNA-sequencing identified previously unknown epithelial subpopulations that were present in both tumor types. In tumors with inhibited IGF1R, a previously undescribed epithelial population marked by expression of both Krt14 and Krt6a was identified, transcriptionally distinct from its MMTV-Wnt1 counterpart, and present in the smallest lung metastases. In human breast cancer patients, expression levels of KRT14 and KRT6A negatively correlated with expression of IGF1R. Conclusions: Inhibition of the IGF1R in a mouse model of basal-like breast cancer produces transcriptionally distinct Krt6a+/Krt14+ epithelial cells, which are present in the smallest metastatic lesions identified in the lung. Expression of genes associated with this population may potentially be effective biomarkers of metastatic capacity in basal-like breast tumors with low levels of IGF1R expression. Full article
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Review

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34 pages, 3909 KB  
Review
Circulating microRNAs at the Interface of Obesity and Breast Cancer: From Molecular Machinery, Diagnostic Potential, and Therapeutic Perspectives
by Georgina Victoria-Acosta, Stephanie I. Núñez-Olvera, María Elizbeth Alvarez-Sánchez, Yarely M. Salinas-Vera and Jonathan Puente-Rivera
Cancers 2026, 18(18), 3035; https://doi.org/10.3390/cancers18183035 - 18 Sep 2026
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Abstract
Obesity influences breast cancer risk, progression, and therapeutic response through endocrine, inflammatory, metabolic, stromal, and vesicular mechanisms. Circulating and extracellular vesicle (EV)-associated microRNAs are attractive liquid biopsy candidates; however, in obesity-associated breast cancer, they should not be interpreted as tumor-only biomarkers. This narrative [...] Read more.
Obesity influences breast cancer risk, progression, and therapeutic response through endocrine, inflammatory, metabolic, stromal, and vesicular mechanisms. Circulating and extracellular vesicle (EV)-associated microRNAs are attractive liquid biopsy candidates; however, in obesity-associated breast cancer, they should not be interpreted as tumor-only biomarkers. This narrative review analyzes circulating/EV-miRNAs as mixed host–tumor signals and separates association-based biomarker evidence from functional EV-mediated transfer. We performed a narrative and integrative review of studies on miRNA biogenesis, circulating miRNA transport, EV biology, adipose tissue dysfunction, adipose-tumor communication, biomarker development, therapy response, and methodological reporting standards. The current literature is read along two independent axes: human relevance and source attribution, from non-breast models to obesity-stratified human cohorts, and mechanistic causality, from association only to EV-level function, miRNA-level function, and causality with rescue; clinical validation is treated as a separate qualifier rather than as the top of a single scale. For example, EV-let-7a in overweight/obese breast cancer patients mainly supports an obesity-stratified biomarker candidate. Breast adipose tissue-derived EV cargoes enriched in miR-155-5p, miR-10a-3p, and miR-30a-3p provide stronger functional support for metabolic reprogramming, whereas EV-associated miR-221/222 has mediator-level evidence in endocrine resistance but is not obesity specific. Conclusions: The main contribution of this review is an operational interpretation framework in which circulating miRNAs are evaluated according to probable source, evidence level, and clinical purpose. Future studies should report EV workflow quality, sample type, hemolysis and platelet control, normalization strategy, external validation, tumor subtype, and obesity phenotyping beyond BMI, including waist circumference or waist-to-hip ratio, insulin resistance, diabetes, menopausal status, and inflammatory markers. Full article
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