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Insights into the Pathogenesis, Molecular Landscape and Therapeutics of Triple-Negative Breast Cancer

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 July 2026 | Viewed by 3483

Special Issue Editor

Dr. Rebecca Chin

E-Mail Website
Guest Editor
Department of Biomedical Sciences and Tung Biomedical Sciences Centre, City University of Hong Kong, Kowloon Tong, Hong Kong
Interests: signaling pathways; solid tumors
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Triple-negative breast cancer (TNBC) remains one of the most aggressive and challenging subtypes of breast cancer, characterized by poor prognosis and high recurrence rates. Despite advances in understanding molecular mechanisms of TNBC, effective treatment options are still lacking. This Special Issue “Insights into the Pathogenesis, Molecular Landscape and Therapeutics of Triple-Negative Breast Cancer” of the International Journal of Molecular Sciences aims to provide an updated overview of basic and translational research on novel insights into TNBC's etiology, molecular signatures, and innovative therapeutic approaches. We invite submissions that employ in vitro, in vivo, and patient-derived organoid models, as well as multi-omics and high-throughput screening approaches, that uncover the complex interplay and clinical implications of genetic, epigenetic, and environmental factors driving the disease.

Dr. Rebecca Chin
Guest Editor

Manuscript Submission Information

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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.

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Keywords

  • breast cancer
  • cancer stemness
  • therapeutic resistance
  • brain metastasis
  • epigenetic mechanisms
  • chromatin remodeling
  • multi-omics approaches
  • high-throughput screening
  • patient-derived organoids

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Published Papers (3 papers)

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Research

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10 pages, 3056 KB  
Article
Low Expression of UBE2Z, a Target Protein of miR-500a, Is Associated with Poor Prognosis in Triple-Negative Breast Cancer
by Donghyun Kim and Song-Yi Choi
Int. J. Mol. Sci. 2026, 27(1), 361; https://doi.org/10.3390/ijms27010361 - 29 Dec 2025
Viewed by 626
Abstract
Triple-negative breast cancer (TNBC) exhibits diverse histological and molecular characteristics. TNBC patients also have the poorest prognoses among those with various breast cancer subtypes, and no effective treatment strategy has been established for TNBC beyond non-specific chemotherapy. Recent studies have reported that the [...] Read more.
Triple-negative breast cancer (TNBC) exhibits diverse histological and molecular characteristics. TNBC patients also have the poorest prognoses among those with various breast cancer subtypes, and no effective treatment strategy has been established for TNBC beyond non-specific chemotherapy. Recent studies have reported that the dysregulation of miRNAs is associated with tumor behavior, prognosis, and treatment responses in TNBC patients. Therefore, this study was conducted to identify miRNAs and key target proteins potentially associated with TNBC prognosis. Fresh-frozen tissue from relapsing and non-relapsing TNBC cases was examined for differentially expressed miRNAs using the Affymetrix GeneChip miRNA 4.0 array, while target genes and proteins were predicted using the miRwalk 2.0 database. The clinical significance of each differentially expressed miRNA was evaluated using the BreastMark database. Additional bioinformatics analyses were conducted to reveal associations with tumor-related signaling pathways; these analyses included protein–protein interaction network construction and Kyoto Encyclopedia of Genes and Genomes pathway annotation. Gene chip analysis identified three upregulated miRNAs (miR-500a, miR-501-3p, and miR-502-3p) and two downregulated miRNAs (miR-6798-5p and miR-7150) in patients with recurrence, and further bioinformatics analyses revealed that target proteins were significantly associated with cell cycle pathways. In addition, low expression of the miR-500a target protein UBE2Z was significantly associated with a poor prognosis. The expression levels of miR-500a and UBE2Z might be useful prognostic biomarkers in TNBC. Full article
(This article belongs to the Special Issue Insights into the Pathogenesis, Molecular Landscape and Therapeutics of Triple-Negative Breast Cancer)
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11 pages, 1715 KB  
Article
Role of ERβ in Triple-Negative Breast Cancer Associated with p53 and Androgen Receptor
by Kei Ito, Naoko Honma, Hideaki Ogata, Akimitsu Yamada, Mika Miyashita, Tomio Arai, Eiichi Sasaki, Kazutoshi Shibuya, Tetuo Mikami and Masataka Sawaki
Int. J. Mol. Sci. 2025, 26(23), 11459; https://doi.org/10.3390/ijms262311459 - 26 Nov 2025
Viewed by 850
Abstract
In triple-negative breast cancer (TNBC), the clinicopathological significance of the expression of a second estrogen receptor, ERβ, remains unclear. Further, although the clinicopathological significance of mutant p53 and androgen receptor (AR) has been investigated in TNBC, they have not been established as therapeutic [...] Read more.
In triple-negative breast cancer (TNBC), the clinicopathological significance of the expression of a second estrogen receptor, ERβ, remains unclear. Further, although the clinicopathological significance of mutant p53 and androgen receptor (AR) has been investigated in TNBC, they have not been established as therapeutic targets. Experimental studies reported the importance of cross-talk between ERβ and p53 or AR in TNBC. In this study, we immunohistochemically examined ERβ expression in surgical specimens of TNBC obtained from postmenopausal patients who underwent surgery without neoadjuvant therapy and investigated the relationship between ERβ expression and various clinicopathological factors, including clinical outcome, while also considering p53 and AR. No significant difference in clinical outcome was noted according to the ERβ status alone (p = 0.2908). However, the ERβ status did affect the relationship between the clinical outcome and p53 or AR status; p53-positive or AR-positive group exhibited significantly more favorable clinical outcomes than p53-negative or AR-negative group, respectively, in the ERβ-positive group (p53, p = 0.0265; AR, p = 0.0285), but not in the ERβ-negative group (p53, p = 0.7228; AR, p = 0.7734). This may be the result of a functional interaction between ERβ and p53 or AR. The role of ERβ in TNBC will be elucidated in further complex studies considering multiple molecules. Full article
(This article belongs to the Special Issue Insights into the Pathogenesis, Molecular Landscape and Therapeutics of Triple-Negative Breast Cancer)
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Review

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24 pages, 4646 KB  
Review
Lipocalin-2 in Triple-Negative Breast Cancer: A Review of Its Pathophysiological Role in the Metastatic Cascade
by Diandra T. Keller, Ralf Weiskirchen and Sarah K. Schröder-Lange
Int. J. Mol. Sci. 2025, 26(22), 10938; https://doi.org/10.3390/ijms262210938 - 12 Nov 2025
Cited by 1 | Viewed by 1507
Abstract
Lipocalin-2 (LCN2) is a 25 kDa glycoprotein that has been shown to be a multifunctional player in the metastasis of triple-negative breast cancer (TNBC). In physiological contexts, LCN2 exhibits bacteriostatic properties and plays key roles in iron homeostasis and the transport of hydrophobic [...] Read more.
Lipocalin-2 (LCN2) is a 25 kDa glycoprotein that has been shown to be a multifunctional player in the metastasis of triple-negative breast cancer (TNBC). In physiological contexts, LCN2 exhibits bacteriostatic properties and plays key roles in iron homeostasis and the transport of hydrophobic molecules. However, several studies have shown that aberrant LCN2 expression is associated with poor prognosis in various malignancies, including breast cancer, which is the most common cancer in women worldwide and can be classified into four molecular subtypes. Among these, TNBC represents a disproportionately aggressive subtype characterized by poor prognosis and high metastatic potential. Although LCN2 has been extensively studied in breast cancer overall, its specific role in TNBC progression and metastasis is only beginning to be understood. Recent evidence suggests that LCN2 contributes to several tumor-promoting processes such as angiogenesis, therapy resistance and modulation of the tumor microenvironment. Moreover, LCN2 appears to influence organ-specific metastasis, particularly to the lung and brain, while its role in liver and bone dissemination remains unclear. Collectively, current data identify LCN2 as a critical mediator of TNBC progression and highlight its potential as a prognostic factor and modulator of disease progression. This review aims to summarize insights from both in vitro and in vivo studies, with particular focus on the role of LCN2 in the metastatic cascade, while also addressing existing research gaps and critically evaluating the current findings. Full article
(This article belongs to the Special Issue Insights into the Pathogenesis, Molecular Landscape and Therapeutics of Triple-Negative Breast Cancer)
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