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Cells
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Biomarkers in Breast Cancer
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Biomarkers in Breast Cancer

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cellular Pathology".

Deadline for manuscript submissions: closed (10 November 2025) | Viewed by 3636

Special Issue Editors

Dr. Julie Decock

E-Mail Website
Guest Editor
1. Translational Oncology Research Center (TORC), Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation (QF), Doha P.O. Box 34110, Qatar
2. College of Health and Life Sciences (CHLS), Hamad Bin Khalifa University (HBKU), Qatar Foundation (QF), Doha P.O. Box 34110, Qatar
Interests: breast cancer; cancer testis antigens; tumor immune microenvironment; tumor target discovery
Dr. Sana A. Bentebbal

E-Mail Website
Guest Editor
Translational Oncology Research Center (TORC), Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation (QF), Doha P.O. Box 34110, Qatar
Interests: cancer-testis antigens; biomarkers in breast cancer

Special Issue Information

Dear Colleagues,

Breast cancer remains a leading cause of cancer-related mortality in women worldwide, with significant heterogeneity in molecular subtypes, disease progression, and treatment responses. Biomarkers play a crucial role in early detection, prognosis, and personalized therapy, yet challenges persist in translating discoveries into clinical practice. Many candidates require further in vivo validation and assessment in diverse patient cohorts to establish their clinical relevance. Addressing these gaps is essential to integrating biomarkers into precision oncology and improving patient outcomes.

This Special Issue of Cells invites original research and reviews on emerging breast cancer biomarkers, with a focus on:

  • Multi-Omics Biomarkers: Integration of genomics, proteomics, epigenomics, and metabolomics to identify novel diagnostic, prognostic, and predictive biomarkers.
  • Liquid Biopsy and Extracellular Vesicles Biomarkers: Advances in circulating tumor DNA (ctDNA), and exosome-derived biomarkers for non-invasive monitoring of disease progression and treatment response.
  • Artificial Intelligence in Biomarker Discovery: AI-driven approaches to identify clinically relevant biomarkers to enhance early detection and patient stratification for therapy selection.
  • Tumor Microenvironment and Immune Signatures: Single-cell and spatial transcriptomic approaches to identify immune-related prognostic and predictive biomarkers.

This Special Issue aims to bridge the gap between biomarker research and clinical translation. We welcome contributions that push the boundaries of precision oncology.

Dr. Julie Decock
Dr. Sana A. Bentebbal
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. Cells 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 2700 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

  • breast cancer biomarkers
  • AI in oncology
  • multi-omics
  • exosomes
  • tumor immune microenvironment
  • liquid biopsy
  • precision oncology
  • personalized medicine

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Published Papers (3 papers)

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Research

19 pages, 2529 KB  
Article
Stress-Inducible Transcription Factor NUPR1 Is Involved in the Inhibitory Effects Exerted by Statins on Insulin Action in ER-Positive Breast Cancer Cells
by Domenica Scordamaglia, Azzurra Zicarelli, Francesca Cirillo, Marianna Talia, Ernestina Marianna De Francesco, Roberta Malaguarnera, Marcello Maggiolini and Rosamaria Lappano
Cells 2026, 15(3), 284; https://doi.org/10.3390/cells15030284 - 2 Feb 2026
Viewed by 727
Abstract
Obesity is frequently associated with metabolic alterations like hypercholesterolemia and hyperinsulinemia and represents a major risk factor for several diseases, including breast cancer (BC). Insulin signaling, as well as the frequent overexpression of the insulin receptor (IR), play a key role in BC [...] Read more.
Obesity is frequently associated with metabolic alterations like hypercholesterolemia and hyperinsulinemia and represents a major risk factor for several diseases, including breast cancer (BC). Insulin signaling, as well as the frequent overexpression of the insulin receptor (IR), play a key role in BC progression. Emerging evidence suggests that the widely prescribed lipid-lowering drugs, named statins, may reduce the risk of recurrence and blunt BC cell proliferation, mainly inhibiting the HMGCR-dependent activation of the mevalonate pathway. In this study, we investigated the effects of simvastatin, atorvastatin and rosuvastatin in BC cells stimulated by insulin. To this end, we used as a BC model system MCF7 cells and naturally immortalized BCAHC-1 cells, which are characterized by high IR-expression levels. Our investigation demonstrates that statins reduce the proliferation and clonogenic capacity of BC cells prompted by insulin treatment. Mechanistically, statins impair the IR-mediated signaling and downregulate the stress-inducible transcription factor NUPR1, a known regulator of cancer progression. Importantly, NUPR1 inhibition blunted the stimulatory action of insulin on BC cells. Consistent with these findings, survival analyses of large cohorts of patients revealed that high levels of NUPR1 are associated with poor BC prognosis. Overall, our results provide novel mechanistic evidence supporting the repositioning of statins in BC, particularly in tumors characterized by elevated IR expression and activity. Full article
(This article belongs to the Special Issue Biomarkers in Breast Cancer)
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17 pages, 3511 KB  
Article
Identification of Resistance Genes in Breast Cancer Cells Treated with Fulvestrant and Ribociclib via Retroviral Screening and Integration Site Sequencing
by Zhangzan Huang, Corine Beaufort, Jean Helmijr, Brian Zantboer, Giada Rozema, Camilla Muritti, Julia J. Whien, Anna Uijterwegen, Michele Massimino, John W. M. Martens and Maurice P. H. M. Jansen
Cells 2026, 15(3), 260; https://doi.org/10.3390/cells15030260 - 29 Jan 2026
Viewed by 865
Abstract
Around 30% of patients with hormone receptor-positive (HR+) breast cancer acquire resistance to endocrine therapy combined with cyclin-dependent kinase 4/6 inhibitors (CDK4/6i), which are first-line treatments in metastatic settings. Therefore, we aimed to identify loci associated with resistance to endocrine therapy and CDK4/6i; [...] Read more.
Around 30% of patients with hormone receptor-positive (HR+) breast cancer acquire resistance to endocrine therapy combined with cyclin-dependent kinase 4/6 inhibitors (CDK4/6i), which are first-line treatments in metastatic settings. Therefore, we aimed to identify loci associated with resistance to endocrine therapy and CDK4/6i; this was achieved using retroviral vectors, which randomly insert gene-disrupting elements into the genome, causing gene expression alterations and potentially leading to therapy resistance. ER-positive ZR75.1 breast cancer cells transduced with retroviral vectors were treated with endocrine (tamoxifen, fulvestrant) or CDK4/6i monotherapies (abemaciclib, palbociclib, ribociclib) or a combination of fulvestrant and ribociclib. DNA was extracted, and virus integration sites (VISs) were characterized according to the detection frequency and read depth using next-generation sequencing (VIS-NGS). Resistance-associated VIS loci were identified when differentially presented in treated samples compared to controls. Well-established tamoxifen resistance genes (BCAR1, BCAR3, EGFR) were detected, enabling the validation of our approach. Thirty-seven VIS loci were associated with resistance to fulvestrant and ribociclib monotherapies. Twenty of these loci were also identified as candidates for resistance to other CDK4/6i and to fulvestrant and ribociclib combination therapy, including TRPS1 and TRIM24—genes that are involved in resistance to endocrine therapy but have not yet been associated with resistance to CDK4/6i. The identification of unique and shared resistance-associated loci highlights the complexity of resistance pathways. Full article
(This article belongs to the Special Issue Biomarkers in Breast Cancer)
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Figure 1

23 pages, 6264 KB  
Article
Prognostic Significance of Macrophage Phenotypes in Peri-Tumoral Normal Tissue of Early-Stage Breast Cancer
by Marcel Hirschmann, Sören Schnellhardt, Matthias Rübner, Sarah Segelhorst, Oliver Ott, Ramona Erber, Christoph Daniel, Maike Büttner-Herold, Paul Gass, Rainer Fietkau and Luitpold Distel
Cells 2025, 14(11), 828; https://doi.org/10.3390/cells14110828 - 3 Jun 2025
Cited by 1 | Viewed by 1470
Abstract
In recent years, tumor-infiltrating inflammatory cells within the tumor microenvironment have been extensively studied. However, much less is known about inflammatory cells in the normal tissue surrounding tumors. In this study, we assess the prognostic significance of tumor-associated macrophages (TAMs) in relation to [...] Read more.
In recent years, tumor-infiltrating inflammatory cells within the tumor microenvironment have been extensively studied. However, much less is known about inflammatory cells in the normal tissue surrounding tumors. In this study, we assess the prognostic significance of tumor-associated macrophages (TAMs) in relation to disease-free survival (DFS) in patients with early-stage breast cancer. Our cohorts included patients from the APBI and BBCC trials, with eligible tumors being small in size and showing no signs of metastasis. We analyzed eight distinct inflammatory cell types in the normal tissue surrounding tumors, with a particular focus on the various macrophage subsets. There were clear differences in the frequencies of the different inflammatory cells, with a higher abundance of cells being found in the intraepithelial compartment compared to the stromal compartment. Notably, we found that M2-type macrophages located in the stromal compartment of tumor distant normal tissue exhibited a positive prognostic impact, in contrast to the M2-type macrophages found within the tumor itself. In the normal tissue surrounding tumors, there are surprisingly clear prognostic predictions for DFS. Normal tissue surrounding breast cancer tumors is clearly influenced by the tumor and could also influence the tumor in terms of growth and metastasis. Tumor-influenced inflammatory cells in the surrounding normal tissue could prevent the immune system from acting against the tumor and promote tumor growth through inflammation. Full article
(This article belongs to the Special Issue Biomarkers in Breast Cancer)
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