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Targeting Breast Cancer: Strategies and Hope—2nd Edition
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Targeting Breast Cancer: Strategies and Hope—2nd Edition

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 20 April 2025 | Viewed by 7375

Special Issue Editors

Prof. Dr. Flora Zagouri

E-Mail Website
Guest Editor
Department of Clinical Therapeutics, Alexandra Hospital, Medical School, 11528 Athens, Greece
Interests: tumors; prognostic markers; antineoplastic agents; cancer biomarkers; tumor biology
Special Issues, Collections and Topics in MDPI journals
Dr. Michalis Liontos

E-Mail Website
Guest Editor
Department of Clinical Therapeutics, Division of Oncology, National and Kapodistrian University of Athens, Alexandra Hospital, 10679 Athens, Greece
Interests: ovarian cancer; uterine cancer; gestational trophoblastic disease; clinical trials
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Christos Papadimitriou

E-Mail
Guest Editor
Second Department of Surgery, Aretaieion Hospital, Medical School, National and Kapodistrian University of Athens, 11528 Athens, Greece
Interests: early breast cancer; adjuvant chemotherapy; chemotherapy for metastatic breast cancer; clinical trials; mTOR inhibitors; CDK4/6 inhibitors; endocrine therapy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Breast cancer therapeutics has evolved rapidly within the last decade as a result of the improvements in the understanding of the molecular biology of the disease. Novel drugs have significantly increased rates of disease-free survival and overall survival of the patients. In parallel, we have recognized categories of patients where de-intensification of treatment results to similar oncological outcomes while sparing patients from toxicities related to treatment. However, there is still an unmet need to improve treatments, especially for more aggressive histologies of the disease.

Regarding hormone receptor positive patients, CDK4/6 inhibitors have revolutionized treatment of metastatic as well as locally advanced disease. Unfortunately, mechanisms of primary and secondary resistance to these agents and hormonal therapy lead to disease recurrence. Further research on molecular alterations that lead to treatment failure as well as proper selection of group of patients is necessary to improve the benefits of this class of drugs. In addition, molecular data that could guide us regarding treatment sequence and possible combinatorial approaches could be of benefit.

For the Her-2 positive group of patients, antibody drug conjugates have significantly extended overall survival in patients with metastatic disease and are currently tested in the adjuvant setting as well. In addition, the efficacy of trastuzumab deruxtacan in patients with low expression of Her-2 triggers scientific research on redefining the population of patients that derive benefit from such agents. Finally, mechanisms of resistance in these drugs as well as biomarkers that could determine proper sequencing of anti-Her2 treatment are of utmost importance.

Finally, in patients with triple negative breast cancer, immunotherapy has provided novel therapeutic opportunities and increased overall survival. Despite early success, though, further understanding of the molecular biology of the disease could provide insight for combinations of immunotherapeutic and targeted agents that could further improve responses and prolong survival. It is also crucial to recognize molecular subtypes of TNBC and guide proper management with the existing agents.

All the above denote that a new, fascinating era has begun regarding the molecular research of breast cancer. The current Special Issue welcomes innovative research that could further promote our knowledge in this field and lead to the development of novel therapeutic agents. Since molecular biology and basic scientific studies are indispensable for the development of our journal, we will prioritize basic research over clinical trials/data.

Prof. Dr. Flora Zagouri
Dr. Michalis Liontos
Prof. Dr. Christos Papadimitriou
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 100 words) can be sent to the Editorial Office for announcement on this website.

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.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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
  • novel drugs
  • hormone receptor
  • inhibitor
  • immunotherapy
  • targeted agents

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Published Papers (3 papers)

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Research

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26 pages, 10062 KiB  
Article
Identifying Key Genes Involved in Axillary Lymph Node Metastasis in Breast Cancer Using Advanced RNA-Seq Analysis: A Methodological Approach with GLMQL and MAS
by Mostafa Rezapour, Robert Wesolowski and Metin Nafi Gurcan
Int. J. Mol. Sci. 2024, 25(13), 7306; https://doi.org/10.3390/ijms25137306 - 3 Jul 2024
Cited by 1 | Viewed by 1547
Abstract
Our study aims to address the methodological challenges frequently encountered in RNA-Seq data analysis within cancer studies. Specifically, it enhances the identification of key genes involved in axillary lymph node metastasis (ALNM) in breast cancer. We employ Generalized Linear Models with Quasi-Likelihood (GLMQLs) [...] Read more.
Our study aims to address the methodological challenges frequently encountered in RNA-Seq data analysis within cancer studies. Specifically, it enhances the identification of key genes involved in axillary lymph node metastasis (ALNM) in breast cancer. We employ Generalized Linear Models with Quasi-Likelihood (GLMQLs) to manage the inherently discrete and overdispersed nature of RNA-Seq data, marking a significant improvement over conventional methods such as the t-test, which assumes a normal distribution and equal variances across samples. We utilize the Trimmed Mean of M-values (TMMs) method for normalization to address library-specific compositional differences effectively. Our study focuses on a distinct cohort of 104 untreated patients from the TCGA Breast Invasive Carcinoma (BRCA) dataset to maintain an untainted genetic profile, thereby providing more accurate insights into the genetic underpinnings of lymph node metastasis. This strategic selection paves the way for developing early intervention strategies and targeted therapies. Our analysis is exclusively dedicated to protein-coding genes, enriched by the Magnitude Altitude Scoring (MAS) system, which rigorously identifies key genes that could serve as predictors in developing an ALNM predictive model. Our novel approach has pinpointed several genes significantly linked to ALNM in breast cancer, offering vital insights into the molecular dynamics of cancer development and metastasis. These genes, including ERBB2, CCNA1, FOXC2, LEFTY2, VTN, ACKR3, and PTGS2, are involved in key processes like apoptosis, epithelial–mesenchymal transition, angiogenesis, response to hypoxia, and KRAS signaling pathways, which are crucial for tumor virulence and the spread of metastases. Moreover, the approach has also emphasized the importance of the small proline-rich protein family (SPRR), including SPRR2B, SPRR2E, and SPRR2D, recognized for their significant involvement in cancer-related pathways and their potential as therapeutic targets. Important transcripts such as H3C10, H1-2, PADI4, and others have been highlighted as critical in modulating the chromatin structure and gene expression, fundamental for the progression and spread of cancer. Full article
(This article belongs to the Special Issue Targeting Breast Cancer: Strategies and Hope—2nd Edition)
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25 pages, 6223 KiB  
Article
FEN1 Inhibition as a Potential Novel Targeted Therapy against Breast Cancer and the Prognostic Relevance of FEN1
by Johanna Berfelde, Laura S. Hildebrand, Lukas Kuhlmann, Rainer Fietkau and Luitpold V. Distel
Int. J. Mol. Sci. 2024, 25(4), 2110; https://doi.org/10.3390/ijms25042110 - 9 Feb 2024
Cited by 1 | Viewed by 2335
Abstract
To improve breast cancer treatment and to enable new strategies for therapeutic resistance, therapeutic targets are constantly being studied. Potential targets are proteins of DNA repair and replication and genomic integrity, such as Flap Endonuclease 1 (FEN1). This study investigated the effects of [...] Read more.
To improve breast cancer treatment and to enable new strategies for therapeutic resistance, therapeutic targets are constantly being studied. Potential targets are proteins of DNA repair and replication and genomic integrity, such as Flap Endonuclease 1 (FEN1). This study investigated the effects of FEN1 inhibitor FEN1-IN-4 in combination with ionizing radiation on cell death, clonogenic survival, the cell cycle, senescence, doubling time, DNA double-strand breaks and micronuclei in breast cancer cells, breast cells and healthy skin fibroblasts. Furthermore, the variation in the baseline FEN1 level and its influence on treatment prognosis was investigated. The cell lines show specific response patterns in the aspects studied and have heterogeneous baseline FEN1 levels. FEN1-IN-4 has cytotoxic, cytostatic and radiosensitizing effects, expressed through increasing cell death by apoptosis and necrosis, G2M share, senescence, double-strand breaks and a reduced survival fraction. Nevertheless, some cells are less affected by the cytotoxicity and fibroblasts show a rather limited response. In vivo, high FEN1 mRNA expression worsens the prognosis of breast cancer patients. Due to the increased expression in breast cancer tissue, FEN1 could represent a new tumor and prognosis marker and FEN1-IN-4 may serve as a new potent agent in personalized medicine and targeted breast cancer therapy. Full article
(This article belongs to the Special Issue Targeting Breast Cancer: Strategies and Hope—2nd Edition)
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Review

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29 pages, 1595 KiB  
Review
Unraveling Biomarker Signatures in Triple-Negative Breast Cancer: A Systematic Review for Targeted Approaches
by Paola Pastena, Hiran Perera, Alessandro Martinino, William Kartsonis and Francesco Giovinazzo
Int. J. Mol. Sci. 2024, 25(5), 2559; https://doi.org/10.3390/ijms25052559 - 22 Feb 2024
Cited by 3 | Viewed by 2832
Abstract
Triple-negative breast cancer (TNBC) is one of the most aggressive subtypes of breast cancer, marked by poor outcomes and dismal prognosis. Due to the absence of targetable receptors, chemotherapy still represents the main therapeutic option. Therefore, current research is now focusing on understanding [...] Read more.
Triple-negative breast cancer (TNBC) is one of the most aggressive subtypes of breast cancer, marked by poor outcomes and dismal prognosis. Due to the absence of targetable receptors, chemotherapy still represents the main therapeutic option. Therefore, current research is now focusing on understanding the specific molecular pathways implicated in TNBC, in order to identify novel biomarker signatures and develop targeted therapies able to improve its clinical management. With the aim of identifying novel molecular features characterizing TNBC, elucidating the mechanisms by which these molecular biomarkers are implicated in the tumor development and progression, and assessing the impact on cancerous cells following their inhibition or modulation, we conducted a literature search from the earliest works to December 2023 on PubMed, Scopus, and Web Of Science. A total of 146 studies were selected. The results obtained demonstrated that TNBC is characterized by a heterogeneous molecular profile. Several biomarkers have proven not only to be characteristic of TNBC but also to serve as potential effective therapeutic targets, holding the promise of a new era of personalized treatments able to improve its prognosis. The pre-clinical findings that have emerged from our systematic review set the stage for further investigation in forthcoming clinical trials. Full article
(This article belongs to the Special Issue Targeting Breast Cancer: Strategies and Hope—2nd Edition)
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