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Cancers
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Advances in TNBC: New Markers for Innovative Treatments
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Advances in TNBC: New Markers for Innovative Treatments

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

Deadline for manuscript submissions: 15 December 2024 | Viewed by 3274

Special Issue Editor

Dr. Pia Giovannelli

E-Mail Website
Guest Editor
Department of Precision Medicine, University of Campania "L. Vanvitelli", 80138 Naples, Italy
Interests: castration-resistant prostate cancer (CRPC); extracellular vesicles; sex steroid hormones in cancers (breast, prostate, pancreatic and colon); triple negative breast cancer; sex steroid receptors; growth factor receptors signaling
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Triple-negative breast cancer (TNBC) is a breast cancer (BC) subtype characterized by the lack of estrogen receptor (ER), progesterone receptor (PR), and the absence of type 2 epidermal growth factor receptor (HER-2) overexpression, the classical markers used in targeted therapy. This feature makes TNBC a hard-to-treat tumor for the meager choice of effective drugs. To date, chemotherapy is the first-line treatment but, unfortunately, many TNBCs only partially respond to it.

For these reasons, TNBC represents a challenge for scientists and physicians. Many studies tried to characterize this BC subtype to find new targetable proteins to cure it and the results have certainly underlined its high heterogeneity as a principal and undisputed trait.

Many molecules, such as EGFR, PI3K, PARP, MEK, and histone deacetylase (HDAC), are mutated or hyperactivated, while others, for instance, AR and ERb, control growth and spreading, thereby all representing an attractive target to develop effective therapies in TNBC. Another weakness of TNBC is the presence of many immune cells, such as tumor-infiltrating lymphocytes, thereby immunotherapy represents another fascinating weapon to treat this incurable cancer.

This Special Issue aims to be a collection of manuscripts useful in updating knowledge on TNBC, and giving new ideas for studying, developing, and testing new drugs, effective even on more aggressive forms of this BC subtype.

I would like to invite you to contribute to this Special Issue with your research articles and reviews that include but are not limited to the following topics: molecular targets, signaling pathways, miRs, the role of epigenetics, new drugs, and targeted treatments in TNBC.

Dr. Pia Giovannelli
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.

Keywords

  • TNBC treatment
  • TNBC target
  • signaling pathways in TNBC
  • epigenetic modifications in TNBC
  • immunotherapy
  • personalized medicine

Published Papers (3 papers)

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34 pages, 10960 KiB  
Article
Characterizing the Inflammatory Profile of Neutrophil-Rich Triple-Negative Breast Cancer
by Fatma Al Qutami, Walaa AlHalabi, Aswathy Vijayakumar, Surendra Singh Rawat, Abubakr H. Mossa, Manju Nidagodu Jayakumar, Baila Samreen and Mahmood Y. Hachim
Cancers 2024, 16(4), 747; https://doi.org/10.3390/cancers16040747 - 10 Feb 2024
Viewed by 942
Abstract
Breast cancer (BC) is one of the most common types of cancer in women in the United Arab Emirates. Immunogenic tumours, such as triple-negative breast cancer (TNBC), show increased neutrophil infiltration, which is associated with poor prognosis and limited efficacy of immunotherapy. This [...] Read more.
Breast cancer (BC) is one of the most common types of cancer in women in the United Arab Emirates. Immunogenic tumours, such as triple-negative breast cancer (TNBC), show increased neutrophil infiltration, which is associated with poor prognosis and limited efficacy of immunotherapy. This study aims to investigate in vitro the bidirectional effect of neutrophils on metastatic TNBC (MDA-MB-231) compared to less-metastatic luminal breast cancer (MCF-7) cell lines. We found that BC cells or their conditioned medium (CM) reduced the viability of neutrophil-like cells (HL60). This was supported by increased cellular stress and NETosis in differentiated HL60 cells (dHL60) upon exposure to MDA-MB-231 compared to MCF-7-CM using nucleic acid staining essays. Flow cytometry showed comparable expression of inflammatory markers by polymorphonuclear cells (PMN) when treated with MDA-MB-231-CM and standard polarizing cocktails. Furthermore, MDA-MB-231-CM triggered an inflammatory pattern with evidence of stronger adhesion (CD62L) and degranulation (CD11b and CD66b) phenotypes. The proinflammatory polarization of dHL60 by MDA-MB-231-CM was additionally confirmed by the elevated CD54 expression, myeloperoxidase, and CD11b protein levels, which matched an increased transwell migratory capacity. In conclusion, BC might use neutrophils to their benefit through NETosis and complement system activation, which makes this crosstalk a potential mechanism for understanding tumour progression. Full article
(This article belongs to the Special Issue Advances in TNBC: New Markers for Innovative Treatments)
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15 pages, 1629 KiB  
Article
MicroRNAs Associated with Androgen Receptor and Metastasis in Triple-Negative Breast Cancer
by Mamoun Ahram, Bayan Abu Alragheb, Hassan Abushukair, Randa Bawadi and Maysa Al-Hussaini
Cancers 2024, 16(3), 665; https://doi.org/10.3390/cancers16030665 - 04 Feb 2024
Viewed by 1049
Abstract
It is crucial to identify novel molecular biomarkers and therapeutic targets for triple-negative breast cancer (TNBC). The androgen receptor (AR) is a regulator of TNBC, acting partially via microRNA molecules (miRNAs). In this study, we used PCR arrays to profile the expression of [...] Read more.
It is crucial to identify novel molecular biomarkers and therapeutic targets for triple-negative breast cancer (TNBC). The androgen receptor (AR) is a regulator of TNBC, acting partially via microRNA molecules (miRNAs). In this study, we used PCR arrays to profile the expression of 84 miRNAs in 24 TNBC tissue samples, which were equally classified according to AR expression and/or metastasis. Several bioinformatics tools were then utilized to determine the potentially affected protein targets and signaling pathways. Seven miRNAs were found to be significantly more highly expressed in association with AR expression, including miR-328-3p and miR-489-3p. Increased expression of miR-205-3p was found to be significantly associated with metastasis. Certain miRNAs were specifically found to be differentially expressed in either metastatic or non-metastatic AR-positive tumors. A gene ontology (GO) analysis indicated biological roles in the regulation of transcription, cellular response to DNA damage, and the transforming growth factor-beta (TGF-beta) signaling pathway. The GO analysis also showed enrichment in kinase and transcription factor activities. The TGF-beta and a number of kinase-dependent pathways were also retrieved using the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. This study offers an understanding of the role of AR in TNBC and further implicates miRNAs in mediating the effects of AR on TNBC. Full article
(This article belongs to the Special Issue Advances in TNBC: New Markers for Innovative Treatments)
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13 pages, 231 KiB  
Perspective
Artificial Intelligence for Precision Oncology of Triple-Negative Breast Cancer: Learning from Melanoma
by Ornella Garrone and Caterina A. M. La Porta
Cancers 2024, 16(4), 692; https://doi.org/10.3390/cancers16040692 - 06 Feb 2024
Viewed by 944
Abstract
Thanks to new technologies using artificial intelligence (AI) and machine learning, it is possible to use large amounts of data to try to extract information that can be used for personalized medicine. The great challenge of the future is, on the one hand, [...] Read more.
Thanks to new technologies using artificial intelligence (AI) and machine learning, it is possible to use large amounts of data to try to extract information that can be used for personalized medicine. The great challenge of the future is, on the one hand, to acquire masses of biological data that nowadays are still limited and, on the other hand, to develop innovative strategies to extract information that can then be used for the development of predictive models. From this perspective, we discuss these aspects in the context of triple-negative breast cancer, a tumor where a specific treatment is still lacking and new therapies, such as immunotherapy, are under investigation. Since immunotherapy is already in use for other tumors such as melanoma, we discuss the strengths and weaknesses identified in the use of immunotherapy with melanoma to try to find more successful strategies. It is precisely in this context that AI and predictive tools can be extremely valuable. Therefore, the discoveries and advancements in immunotherapy for melanoma provide a foundation for developing effective immunotherapies for triple-negative breast cancer. Shared principles, such as immune system activation, checkpoint inhibitors, and personalized treatment, can be applied to TNBC to improve patient outcomes and offer new hope for those with aggressive, hard-to-treat breast cancer. Full article
(This article belongs to the Special Issue Advances in TNBC: New Markers for Innovative Treatments)
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