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Cancers
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Molecular Targets and Promising Therapeutics of Triple-Negative Breast Cancer
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Molecular Targets and Promising Therapeutics of Triple-Negative Breast Cancer

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

Deadline for manuscript submissions: closed (20 June 2023) | Viewed by 6662

Special Issue Editors

Dr. Richard G. Pestell

E-Mail Website
Guest Editor
1. Pennsylvania Cancer and Regenerative Medicine Research Center, Baruch S. Blumberg Institute, Doylestown, PA 19096, USA
2. Wistar Institute, Philadelphia, PA 19107, USA
Interests: breast cancer; triple negative breast cancer; cancer immune therapy; cell cycle; CCR5
Dr. Khandan Keyomarsi

E-Mail Website
Guest Editor
Department of Experimental Radiation Oncology, UTMD Anderson Cancer Center, Houston, TX, USA
Interests: regulates autophagy; breast cancer

Special Issue Information

Dear Colleagues,

Breast cancer is a leading cause of cancer morbidity affecting approximately 12% of women worldwide, accounting for 14% of all cancer deaths with more than a million women per year worldwide. Breast cancer can be categorized based on distinct coding sequence characteristics: Luminal A, Luminal B, HER2-overexpressing/enriched (HER2+), normal-like breast cancer (NLBC), and triple-negative/basal-like breast cancer (TNBC). TNBC, which has the worst prognosis, has historically been considered a disease without precise molecular therapeutic options. A growing body of studies indicates that TNBC consists of several subtypes that may warrant specific targeted therapies. 

Important new developments have occurred in the understanding of the pathogenesis, epidemiology, molecular subtyping (coding and non-coding genome), immune responses, and treatment of triple-negative breast cancer. The use of checkpoint inhibitors, PARP inhibitors, CDK inhibitors, and CCR5 inhibitors has suggested the importance of theragnostic markers in trial design to determine the value of specific targeted therapies.

The purpose of this Special Issue is to provide distinct insights into triple-negative breast cancer provided by different fields and coalesce current therapeutic understandings in order to facilitate innovative new therapeutic approaches and further inform clinician and patient decision making.

The understanding of triple-negative breast cancer is a rapidly evolving field with new insights based on molecular interrogation. New therapies have shown promising results warranting an update of current published literature.

Dr. Richard G. Pestell
Dr. Khandan Keyomarsi
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. 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

  • breast cancer
  • triple-negative breast cancer
  • PDL
  • breast cancer disparities
  • immune oncology
  • CCR5
  • G protein coupled receptors

Published Papers (2 papers)

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15 pages, 2430 KiB  
Article
ImmunoPET Imaging Identifies the Optimal Timepoint for Combination Therapy in Xenograft Models of Triple-Negative Breast Cancer
by Ziqi Li, Erika Belitzky, Ondrej Blaha, Alessandra Cavaliere, Samantha R. Katz, Mariam Aboian, Lindy Melegari, Khashayar Rajabimoghadam, Stephen Kurpiewski, Xiaohua Zhu and Bernadette Marquez-Nostra
Cancers 2023, 15(5), 1589; https://doi.org/10.3390/cancers15051589 - 03 Mar 2023
Cited by 1 | Viewed by 2073
Abstract
(1) Purpose: The glycoprotein non-metastatic melanoma B (gpNMB) is a type 1 transmembrane protein that is overexpressed in numerous cancers, including triple-negative breast cancer (TNBC). Its overexpression is associated with lower overall survival of patients with TNBC. Tyrosine kinase inhibitors such as dasatinib [...] Read more.
(1) Purpose: The glycoprotein non-metastatic melanoma B (gpNMB) is a type 1 transmembrane protein that is overexpressed in numerous cancers, including triple-negative breast cancer (TNBC). Its overexpression is associated with lower overall survival of patients with TNBC. Tyrosine kinase inhibitors such as dasatinib can upregulate gpNMB expression, which has the potential to enhance therapeutic targeting with anti-gpNMB antibody drug conjugates such as glembatumumab vedotin (CDX-011). Our primary aim is to quantify the degree and identify the timeframe of gpNMB upregulation in xenograft models of TNBC after treatment with the Src tyrosine kinase inhibitor, dasatinib, by longitudinal positron emission tomography (PET) imaging with the 89Zr-labeled anti-gpNMB antibody ([89Zr]Zr-DFO-CR011). The goal is to identify the timepoint at which to administer CDX-011 after treatment with dasatinib to enhance therapeutic efficacy using noninvasive imaging. (2) Methods: First, TNBC cell lines that either express gpNMB (MDA-MB-468) or do not express gpNMB (MDA-MB-231) were treated with 2 μM of dasatinib in vitro for 48 h, followed by Western blot analysis of cell lysates to determine differences in gpNMB expression. MDA-MB-468 xenografted mice were also treated with 10 mg/kg of dasatinib every other day for 21 days. Subgroups of mice were euthanized at 0-, 7-, 14-, and 21-days post treatment, and tumors were harvested for Western blot analysis of tumor cell lysates for gpNMB expression. In a different cohort of MDA-MB-468 xenograft models, longitudinal PET imaging with [89Zr]Zr-DFO-CR011 was performed before treatment at 0 (baseline) and at 14 and 28 days after treatment with (1) dasatinib alone (2) CDX-011 (10 mg/kg) alone, or (3) sequential treatment of dasatinib for 14 days then CDX-011 to determine changes in gpNMB expression in vivo relative to baseline. As a gpNMB-negative control, MDA-MB-231 xenograft models were imaged 21 days after treatment with dasatinib, combination of CDX-011 and dasatinib, and vehicle control. (3) Results: Western blot analysis of MDA-MB-468 cell and tumor lysates showed that dasatinib increased expression of gpNMB in vitro and in vivo at 14 days post treatment initiation. In PET imaging studies of different cohorts of MDA-MB-468 xenografted mice, [89Zr]Zr-DFO-CR011 uptake in tumors (SUVmean = 3.2 ± 0.3) was greatest at 14 days after treatment initiation with dasatinib (SUVmean = 4.9 ± 0.6) or combination of dasatinib and CDX-011 (SUVmean= 4.6 ± 0.2) compared with that at baseline (SUVmean = 3.2 ± 0.3). The highest tumor regression after treatment was observed in the combination-treated group with a percent change in tumor volume relative to baseline (%CTV) of −54 ± 13 compared with the vehicle control-treated group (%CTV = +102 ± 27), CDX-011 group (%CTV = −25 ± 9.8), and dasatinib group (%CTV = −23 ± 11). In contrast, the PET imaging of MDA-MB-231 xenografted mice indicated no significant difference in the tumor uptake of [89Zr]Zr-DFO-CR011 between treated (dasatinib alone or in combination with CDX-011) and vehicle-control groups. (4) Conclusions: Dasatinib upregulated gpNMB expression in gpNMB-positive MDA-MB-468 xenografted tumors at 14 days post treatment initiation, which can be quantified by PET imaging with [89Zr]Zr-DFO-CR011. Furthermore, combination therapy with dasatinib and CDX-011 appears to be a promising therapeutic strategy for TNBC and warrants further investigation. Full article
(This article belongs to the Special Issue Molecular Targets and Promising Therapeutics of Triple-Negative Breast Cancer)
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Review

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49 pages, 17207 KiB  
Review
Endorsement of TNBC Biomarkers in Precision Therapy by Nanotechnology
by Aiswarya Chaudhuri, Dulla Naveen Kumar, Deepa Dehari, Rohit Patil, Sanjay Singh, Dinesh Kumar and Ashish Kumar Agrawal
Cancers 2023, 15(9), 2661; https://doi.org/10.3390/cancers15092661 - 08 May 2023
Cited by 5 | Viewed by 4013
Abstract
Breast cancer is a heterogeneous disease which accounts globally for approximately 1 million new cases annually, wherein more than 200,000 of these cases turn out to be cases of triple-negative breast cancer (TNBC). TNBC is an aggressive and rare breast cancer subtype that [...] Read more.
Breast cancer is a heterogeneous disease which accounts globally for approximately 1 million new cases annually, wherein more than 200,000 of these cases turn out to be cases of triple-negative breast cancer (TNBC). TNBC is an aggressive and rare breast cancer subtype that accounts for 10–15% of all breast cancer cases. Chemotherapy remains the only therapy regimen against TNBC. However, the emergence of innate or acquired chemoresistance has hindered the chemotherapy used to treat TNBC. The data obtained from molecular technologies have recognized TNBC with various gene profiling and mutation settings that have helped establish and develop targeted therapies. New therapeutic strategies based on the targeted delivery of therapeutics have relied on the application of biomarkers derived from the molecular profiling of TNBC patients. Several biomarkers have been found that are targets for the precision therapy in TNBC, such as EGFR, VGFR, TP53, interleukins, insulin-like growth factor binding proteins, c-MET, androgen receptor, BRCA1, glucocorticoid, PTEN, ALDH1, etc. This review discusses the various candidate biomarkers identified in the treatment of TNBC along with the evidence supporting their use. It was established that nanoparticles had been considered a multifunctional system for delivering therapeutics to target sites with increased precision. Here, we also discuss the role of biomarkers in nanotechnology translation in TNBC therapy and management. Full article
(This article belongs to the Special Issue Molecular Targets and Promising Therapeutics of Triple-Negative Breast Cancer)
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