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The Promise of Precision Oncology in Breast Cancer

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: closed (31 December 2021) | Viewed by 20898

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Special Issue Editor

Dr. Maurizio Callari

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Guest Editor

CRUK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK

Special Issue Information

Dear Colleagues,

Breast cancer remains a leading cause of death among women worldwide. While we acknowledge some of the best examples of targeted treatments exist for this cancer type (i.e., hormone therapy in ER-positive and anti-HER2 treatment in HER2 amplified tumors), we are still far from implementing truly personalized patient management.

Extensive molecular characterization has revealed inter- and intra-tumor heterogeneity as hallmarks of the disease. Similarly, a functionally relevant heterogeneity has been observed in the tumor microenvironment. Such diversity implies the necessity for innovative and tailored therapeutic interventions; however, our understanding of the mechanisms determining treatment response is still unsatisfactory. Technological development has enabled genome-wide measurements, multi-omic approaches and single-cell resolution analysis, providing an unprecedented ability to capture the complexity of cancer as a system. In this context, computational biology has a key and expanding role for the effective exploitation of the increasing amount of data generated.

This Special Issue “The Promise of Precision Oncology in Breast Cancer” of the International Journal of Molecular Sciences will publish a collection of the latest high-quality research papers, contributing to precision oncology in breast cancer patients.

Dr. Maurizio Callari
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. 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
precision oncology
biomarkers
omics
mechanism of resistance
tumor microenvironment
pharmacogenomics
pharmacoproteomics

Published Papers (5 papers)

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Research

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16 pages, 13400 KiB

Open AccessArticle

CLDN6 Suppresses c–MYC–Mediated Aerobic Glycolysis to Inhibit Proliferation by TAZ in Breast Cancer

by Huinan Qu, Da Qi, Xinqi Wang, Yuan Dong, Qiu Jin, Junyuan Wei and Chengshi Quan

Int. J. Mol. Sci. 2022, 23(1), 129; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23010129 - 23 Dec 2021

Cited by 11 | Viewed by 2843

Abstract

Claudin 6 (CLDN6) was found to be a breast cancer suppressor gene, which is lowly expressed in breast cancer and inhibits breast cancer cell proliferation upon overexpression. However, the mechanism by which CLDN6 inhibits breast cancer proliferation is unclear. Here, we investigated this issue and elucidated the molecular mechanisms by which CLDN6 inhibits breast cancer proliferation. First, we verified that CLDN6 was lowly expressed in breast cancer tissues and that patients with lower CLDN6 expression had a worse prognosis. Next, we confirmed that CLDN6 inhibited breast cancer proliferation through in vitro and in vivo experiments. As for the mechanism, we found that CLDN6 inhibited c–MYC–mediated aerobic glycolysis based on a metabolomic analysis of CLDN6 affecting cellular lactate levels. CLDN6 interacted with a transcriptional co–activator with PDZ-binding motif (TAZ) and reduced the level of TAZ, thereby suppressing c–MYC transcription, which led to a reduction in glucose uptake and lactate production. Considered together, our results suggested that CLDN6 suppressed c–MYC–mediated aerobic glycolysis to inhibit the proliferation of breast cancer by TAZ, which indicated that CLDN6 acted as a novel regulator of aerobic glycolysis and provided a theoretical basis for CLDN6 as a biomarker of progression in breast cancer. Full article

(This article belongs to the Special Issue The Promise of Precision Oncology in Breast Cancer)

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18 pages, 3327 KiB

Open AccessArticle

Total Blood Exosomes in Breast Cancer: Potential Role in Crucial Steps of Tumorigenesis

by Maria Konoshenko, Georgy Sagaradze, Evgeniya Orlova, Tatiana Shtam, Ksenia Proskura, Roman Kamyshinsky, Natalia Yunusova, Antonina Alexandrova, Anastasia Efimenko and Svetlana Tamkovich

Int. J. Mol. Sci. 2020, 21(19), 7341; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21197341 - 05 Oct 2020

Cited by 23 | Viewed by 3245

Abstract

Exosomes are crucial players in cell-to-cell communication and are involved in tumorigenesis. There are two fractions of blood circulating exosomes: free and cell-surface-associated. Here, we compared the effect of total blood exosomes (contain plasma exosomes and blood cell-surface-associated exosomes) and plasma exosomes from breast cancer patients (BCPs, n = 43) and healthy females (HFs, n = 35) on crucial steps of tumor progression. Exosomes were isolated by ultrafiltration, followed by ultracentrifugation, and characterized by cryo-electron microscopy (cryo-EM), nanoparticle tracking analysis, and flow cytometry. Cryo-EM revealed a wider spectrum of exosome morphology with lipid bilayers and vesicular internal structures in the HF total blood in comparison with plasma. No differences in the morphology of both exosomes fractions were detected in BCP blood. The plasma exosomes and total blood exosomes of BCPs had different expression levels of tumor-associated miR-92a and miR-25-3p, induced angiogenesis and epithelial-to-mesenchymal transition (EMT), and increased the number of migrating pseudo-normal breast cells and the total migration path length of cancer cells. The multidirectional effects of HF total blood exosomes on tumor dissemination were revealed; they suppress the angiogenesis and total migration path length of MCF10A, but stimulate EMT and increase the number of migrating MCF10A and the total path length of SKBR3 cells. In addition, HF plasma exosomes enhance the metastasis-promoting properties of SKBR3 cells and stimulate angiogenesis. Both cell-free and blood cell-surface-associated exosomes are involved in the crucial stages of carcinogenesis: the initiation of EMT and the stimulation of proliferation, cell migration, and angiogenesis. Thus, for the estimation of the diagnostic/prognostic significance of circulating exosomes in the blood of cancer patients more correctly, the total blood exosomes, which consist of plasma exosomes and blood cell-surface-associated exosomes should be used. Full article

(This article belongs to the Special Issue The Promise of Precision Oncology in Breast Cancer)

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Review

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15 pages, 652 KiB

Open AccessReview

IL-6 Cytokine Family: A Putative Target for Breast Cancer Prevention and Treatment

by Carla M. Felcher, Emilia S. Bogni and Edith C. Kordon

Int. J. Mol. Sci. 2022, 23(3), 1809; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23031809 - 05 Feb 2022

Cited by 22 | Viewed by 4002

Abstract

The IL-6 cytokine family is a group of signaling molecules with wide expression and function across vertebrates. Each member of the family signals by binding to its specific receptor and at least one molecule of gp130, which is the common transmembrane receptor subunit for the whole group. Signal transduction upon stimulation of the receptor complex results in the activation of multiple downstream cascades, among which, in mammary cells, the JAK-STAT3 pathway plays a central role. In this review, we summarize the role of the IL-6 cytokine family—specifically IL-6 itself, LIF, OSM, and IL-11—as relevant players during breast cancer progression. We have compiled evidence indicating that this group of soluble factors may be used for early and more precise breast cancer diagnosis and to design targeted therapy to treat or even prevent metastasis development, particularly to the bone. Expression profiles and possible therapeutic use of their specific receptors in the different breast cancer subtypes are also described. In addition, participation of these cytokines in pathologies of the breast linked to lactation and involution of the gland, as post-partum breast cancer and mastitis, is discussed. Full article

(This article belongs to the Special Issue The Promise of Precision Oncology in Breast Cancer)

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26 pages, 993 KiB

Open AccessReview

Precision Oncology via NMR-Based Metabolomics: A Review on Breast Cancer

by Alessia Vignoli, Emanuela Risi, Amelia McCartney, Ilenia Migliaccio, Erica Moretti, Luca Malorni, Claudio Luchinat, Laura Biganzoli and Leonardo Tenori

Int. J. Mol. Sci. 2021, 22(9), 4687; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22094687 - 28 Apr 2021

Cited by 25 | Viewed by 4407

Abstract

Precision oncology is an emerging approach in cancer care. It aims at selecting the optimal therapy for the right patient by considering each patient’s unique disease and individual health status. In the last years, it has become evident that breast cancer is an extremely heterogeneous disease, and therefore, patients need to be appropriately stratified to maximize survival and quality of life. Gene-expression tools have already positively assisted clinical decision making by estimating the risk of recurrence and the potential benefit from adjuvant chemotherapy. However, these approaches need refinement to further reduce the proportion of patients potentially exposed to unnecessary chemotherapy. Nuclear magnetic resonance (NMR) metabolomics has demonstrated to be an optimal approach for cancer research and has provided significant results in BC, in particular for prognostic and stratification purposes. In this review, we give an update on the status of NMR-based metabolomic studies for the biochemical characterization and stratification of breast cancer patients using different biospecimens (breast tissue, blood serum/plasma, and urine). Full article

(This article belongs to the Special Issue The Promise of Precision Oncology in Breast Cancer)

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20 pages, 1894 KiB

Open AccessReview

Emerging Immunotherapies against Novel Molecular Targets in Breast Cancer

by Vignesh Sivaganesh, Nazifa Promi, Salma Maher and Bela Peethambaran

Int. J. Mol. Sci. 2021, 22(5), 2433; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22052433 - 28 Feb 2021

Cited by 12 | Viewed by 5478

Abstract

Immunotherapy is a highly emerging form of breast cancer therapy that enables clinicians to target cancers with specific receptor expression profiles. Two popular immunotherapeutic approaches involve chimeric antigen receptor-T cells (CAR-T) and bispecific antibodies (BsAb). Briefly mentioned in this review as well is the mRNA vaccine technology recently popularized by the COVID-19 vaccine. These forms of immunotherapy can highly select for the tumor target of interest to generate specific tumor lysis. Along with improvements in CAR-T, bispecific antibody engineering, and therapeutic administration, much research has been done on novel molecular targets that can especially be useful for triple-negative breast cancer (TNBC) immunotherapy. Combining emerging immunotherapeutics with tumor marker discovery sets the stage for highly targeted immunotherapy to be the future of cancer treatments. This review highlights the principles of CAR-T and BsAb therapy, improvements in CAR and BsAb engineering, and recently identified human breast cancer markers in the context of in vitro or in vivo CAR-T or BsAb treatment. Full article

(This article belongs to the Special Issue The Promise of Precision Oncology in Breast Cancer)

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