Innovative Therapeutic Strategies and Molecular Mechanisms in Breast Cancer

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cancer Biology and Oncology".

Deadline for manuscript submissions: 31 January 2027 | Viewed by 1515

Editors


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Guest Editor
The Clinical Department, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania
Interests: breast cancer; gynecological cancer; angiogenesisi; glioma
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
1. "Prof. Dr. Alexandru Trestioreanu" Oncology and Palliative care Discipline, Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania
2. Medical Oncology II Department, "Prof. Dr. Alexandru Trestioreanu" Oncology Institute, 022328 Bucharest, Romania
Interests: breast cancer; cervical cancer; biomarkers; hereditary cancers
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Breast cancer remains one of the most prevalent and complex malignancies worldwide, accounting for a significant proportion of cancer-related morbidity and mortality among women. Advances in molecular biology have unraveled the heterogeneity of breast cancer, revealing diverse subtypes characterized by distinct genetic and molecular profiles. Understanding these molecular mechanisms has paved the way for the development of targeted therapies, which have markedly improved patient outcomes. However, resistance to current treatments and metastatic progression continue to pose major challenges, necessitating innovative therapeutic strategies.

This Special Issue aims to provide a comprehensive overview of innovative approaches—from molecular targets and signaling pathways to emerging treatment modalities—that address the unmet needs in breast cancer therapy. We welcome original research articles and comprehensive reviews focusing on, but not limited to, the following themes:

  • Novel molecular targets and signaling pathways in breast cancer;
  • Development and evaluation of targeted therapies and immunotherapies;
  • Mechanisms of resistance to current treatments;
  • Biomarkers for prognosis and therapy response;
  • Innovative diagnostic and imaging techniques;
  • Preclinical models and translational research;
  • Combination strategies integrating molecular insights;
  • Emerging technologies, such as nanomedicine and gene editing, in breast cancer treatment.

We look forward to receiving your valuable contributions to advance the understanding and treatment of breast cancer through this special collection.

Dr. Oana Gabriela Trifanescu
Dr. Laurentia Nicoleta Gales
Guest Editors

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Keywords

  • breast cancer
  • immunotherapy
  • medical imaging
  • biomarkers
  • translational research

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Published Papers (1 paper)

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Review

50 pages, 2248 KB  
Review
Research Progress of PROTACs in Breast Cancer: Subtype-Oriented Target Landscape, Clinical Stratification Evidence, and Engineering Strategies for Translation
by Senyang Guo, Jianhua Liu, Hongmei Zheng and Xinhong Wu
Biomedicines 2026, 14(4), 835; https://doi.org/10.3390/biomedicines14040835 - 6 Apr 2026
Viewed by 1258
Abstract
Molecular subtype–guided therapy for breast cancer (BC) remains limited in a subset of patients by suboptimal efficacy, acquired resistance, and the presence of “undruggable” targets. Proteolysis-targeting chimeras (PROTACs) represent a targeted protein degradation (TPD) strategy that differs fundamentally from conventional occupancy-driven inhibition. By [...] Read more.
Molecular subtype–guided therapy for breast cancer (BC) remains limited in a subset of patients by suboptimal efficacy, acquired resistance, and the presence of “undruggable” targets. Proteolysis-targeting chimeras (PROTACs) represent a targeted protein degradation (TPD) strategy that differs fundamentally from conventional occupancy-driven inhibition. By inducing ubiquitination of a protein of interest and subsequent proteasomal degradation, PROTACs can directly reduce pathogenic protein abundance and potentially abrogate non-catalytic or scaffolding functions, thereby enabling more durable pathway suppression in selected resistance contexts. This review comprehensively summarizes the mechanisms of action, key molecular design elements, and the developmental landscape of PROTACs, and maps target selection and research progress across BC molecular subtypes. In hormone receptor–positive/HER2-negative BC, clinical translation is most advanced for estrogen receptor alpha-directed PROTACs; Phase III evidence indicates biomarker-dependent efficacy, with clearer benefit signals in resistant subgroups such as estrogen receptor 1 mutations, suggesting that the net clinical benefit of TPD is more likely to be realized through precision stratification. In contrast, in solid-tumor settings, including human epidermal growth factor receptor 2 (HER2)-positive BC and triple-negative breast cancer, PROTAC translation is more frequently constrained by an “exposure–selectivity–therapeutic window” trade-off driven by physicochemical liabilities, insufficient tumor penetration, and broad target expression. Accordingly, engineering strategies—such as antibody/aptamer-mediated targeted delivery, stimulus-responsive prodrugs, nanocarriers, and local administration—are emerging as decisive approaches to enable safe and effective clinical implementation. Looking forward, further progress of PROTACs in BC will depend on expanding the spectrum of E3 ubiquitin ligases and recruitment modalities, establishing predictable and dynamically monitorable biomarker systems, optimizing rational combination/sequencing regimens with exposure- and schedule-guided dosing, and advancing scalable manufacturing and quality control capabilities, thereby translating mechanistic advantages of TPD into verifiable precision-therapy applications. Full article
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