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Cancers
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Advances in Triple-Negative Breast Cancer
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Advances in Triple-Negative Breast Cancer

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Immunology and Immunotherapy".

Deadline for manuscript submissions: closed (10 April 2024) | Viewed by 5191

Special Issue Editor

Dr. Marta Santisteban

E-Mail Website
Guest Editor
Medical Oncology, Breast Cancer Unit, Clínica Universidad de Navarra, 31008 Pamplona, Spain
Interests: breast cancer; triple negative; tumor microenvironment; TILs; immunotherapy, dendritic cells; vaccines; immune check point inhibitors; cancer stem cells; microbiome

Special Issue Information

Dear Colleagues,

Among all breast cancers (BCs), the triple-negative (TN) subtype drives a grim outcome to patients due to its aggressive behavior and the lack of druggable identified targets. In recent years, checkpoint-inhibitor-based immunotherapy has emerged as a new therapy in this biologic subtype that has improved patients’ survival, based on tumor immune signatures, tumor mutational burden, tumor-infiltrating lymphocytes, the PD-L1/PD-1 axis, and other factors related to individual patients. On the other hand, the incorporation of PARP inhibitors, antibody drug conjugates, BC vaccines, and active as well as adoptive cell immunotherapy aims to improve the landscape to treat this population of TNBC patients, both in monotherapy and in combination. All of the new therapeutic strategies have important roles in this scenario, tackling this disease in different ways, which permits the de-escalation of conventional chemotherapy. This Special Issue, entitled “Advances in Triple-Negative Breast Cancer”, aims to approach novel biomarkers and therapeutic strategies to improve patients´ outcomes and quality of life.

Dr. Marta Santisteban
Guest Editor

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. Cancers 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 2900 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.

Published Papers (3 papers)

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Research

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25 pages, 5628 KiB  
Article
Abrogating Metastatic Properties of Triple-Negative Breast Cancer Cells by EGFR and PI3K Dual Inhibitors
by Ana Rita Garcia, Avilson Mendes, Carlos Custódia, Cláudia C. Faria, João T. Barata, Rui Malhó, Inês Figueira and Maria Alexandra Brito
Cancers 2023, 15(15), 3973; https://doi.org/10.3390/cancers15153973 - 4 Aug 2023
Viewed by 1275
Abstract
Triple-negative breast cancer (TNBC) is a devastating BC subtype. Its aggressiveness, allied to the lack of well-defined molecular targets, usually culminates in the appearance of metastases that account for poor prognosis, particularly when they develop in the brain. Nevertheless, TNBC has been associated [...] Read more.
Triple-negative breast cancer (TNBC) is a devastating BC subtype. Its aggressiveness, allied to the lack of well-defined molecular targets, usually culminates in the appearance of metastases that account for poor prognosis, particularly when they develop in the brain. Nevertheless, TNBC has been associated with epidermal growth factor receptor (EGFR) overexpression, leading to downstream phosphoinositide 3-kinase (PI3K) signaling activation. We aimed to unravel novel drug candidates for TNBC treatment based on EGFR and/or PI3K inhibition. Using a highly metastatic TNBC cell line with brain tropism (MDA-MB-231 Br4) and a library of 27 drug candidates in silico predicted to inhibit EGFR, PI3K, or EGFR plus PI3K, and to cross the blood–brain barrier, we evaluated the effects on cell viability. The half maximal inhibitory concentration (IC50) of the most cytotoxic ones was established, and cell cycle and death, as well as migration and EGFR pathway intervenient, were further evaluated. Two dual inhibitors emerged as the most promising drugs, with the ability to modulate cell cycle, death, migration and proliferation, morphology, and PI3K/AKT cascade players such as myocyte enhancer factor 2C (MEF2C) and forkhead box P1 (FOXP1). This work revealed EGFR/PI3K dual inhibitors as strong candidates to tackle brain metastatic TNBC cells. Full article
(This article belongs to the Special Issue Advances in Triple-Negative Breast Cancer)
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0 pages, 3137 KiB  
Article
Targeting and Sensitization of Breast Cancer Cells to Killing with a Novel Interleukin-13 Receptor α2-Specific Hybrid Cytolytic Peptide
by Riaz Jannoo, William Walker and Venkateswarlu Kanamarlapudi
Cancers 2023, 15(10), 2772; https://doi.org/10.3390/cancers15102772 - 16 May 2023
Cited by 3 | Viewed by 2084 | Correction
Abstract
Highly metastatic breast cancers, such as triple-negative subtypes (TNBC), require the most effective treatments. Since interleukin-13 receptor (IL-13R)α2 is reportedly over-expressed in some cancers, we investigated here its expression and the feasibility of therapeutically targeting this receptor in breast cancer using a novel [...] Read more.
Highly metastatic breast cancers, such as triple-negative subtypes (TNBC), require the most effective treatments. Since interleukin-13 receptor (IL-13R)α2 is reportedly over-expressed in some cancers, we investigated here its expression and the feasibility of therapeutically targeting this receptor in breast cancer using a novel hybrid cytolytic peptide (Pep-1-Phor21) consisting of IL-13Rα2-binding (Pep-1) and cytolytic (Phor21) domains. This study demonstrates that particularly TNBC tissues and cells display the prominent expression of IL-13Rα2. Furthermore, Pep-1-Phor21 induced the rapid necrosis of tumor cells expressing cell-surface IL-13Rα2. Notably, IL-13Rα2 expression was found to be epigenetically regulated in breast cancer cells in that the inhibition of histone deacetylase (HDAC) or DNA methyltransferase (DNMT) upregulated IL-13Rα2 expression, thereby sensitizing them to Pep-1-Phor21. IL-13Rα2-negative non-malignant cells were refractory to these epigenetic effects. Consistent with its cytolytic activity, Pep-1-Phor21 readily destroyed IL-13Rα2-expressing breast cancer spheroids with HDAC or DNMT inhibition, further enhancing cytolytic activity. Therefore, the Pep-1-Phor21-mediated targeting of IL-13Rα2 is a potentially novel therapeutic strategy for TNBC. Given that tumor cells can be selectively sensitized to Pep-1-Phor21 via the epigenetic up-regulation of IL-13Rα2, a combined adjuvant approach involving Pep-1-Phor21 and epigenetic inhibitors may be an effective strategy. Full article
(This article belongs to the Special Issue Advances in Triple-Negative Breast Cancer)
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Review

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20 pages, 1932 KiB  
Review
The Transformative Role of 3D Culture Models in Triple-Negative Breast Cancer Research
by Xavier S. Bittman-Soto, Evelyn S. Thomas, Madeline E. Ganshert, Laura L. Mendez-Santacruz and J. Chuck Harrell
Cancers 2024, 16(10), 1859; https://doi.org/10.3390/cancers16101859 - 13 May 2024
Viewed by 1266
Abstract
Advancements in cell culturing techniques have allowed the development of three-dimensional (3D) cell culture models sourced directly from patients’ tissues and tumors, faithfully replicating the native tissue environment. These models provide a more clinically relevant platform for studying disease progression and treatment responses [...] Read more.
Advancements in cell culturing techniques have allowed the development of three-dimensional (3D) cell culture models sourced directly from patients’ tissues and tumors, faithfully replicating the native tissue environment. These models provide a more clinically relevant platform for studying disease progression and treatment responses compared to traditional two-dimensional (2D) models. Patient-derived organoids (PDOs) and patient-derived xenograft organoids (PDXOs) emerge as innovative 3D cancer models capable of accurately mimicking the tumor’s unique features, enhancing our understanding of tumor complexities, and predicting clinical outcomes. Triple-negative breast cancer (TNBC) poses significant clinical challenges due to its aggressive nature, propensity for early metastasis, and limited treatment options. TNBC PDOs and PDXOs have significantly contributed to the comprehension of TNBC, providing novel insights into its underlying mechanism and identifying potential therapeutic targets. This review explores the transformative role of various 3D cancer models in elucidating TNBC pathogenesis and guiding novel therapeutic strategies. It also provides an overview of diverse 3D cell culture models, derived from cell lines and tumors, highlighting their advantages and culturing challenges. Finally, it delves into live-cell imaging techniques, endpoint assays, and alternative cell culture media and methodologies, such as scaffold-free and scaffold-based systems, essential for advancing 3D cancer model research and development. Full article
(This article belongs to the Special Issue Advances in Triple-Negative Breast Cancer)
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