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Cancers
Special Issues
Novel Targets in Triple-Negative Breast Cancer
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Novel Targets in Triple-Negative Breast Cancer

A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: closed (31 August 2021) | Viewed by 10264

Special Issue Editors

Prof. Alberto Ocaña

E-Mail Website
Guest Editor
Centro Regional de Investigaciones Biomédicas (CRIB), Castilla La Mancha University, Albacete, Spain
Interests: breast cancer; novel targets; experimental therapeutics; translational oncology; biomarker discovery
Dr. Atanasio Pandiella

E-Mail Website
Guest Editor
Centro de Investigación del Cáncer (Universidad de Salamanca-CSIC), Campus Universitario Miguel de Unamuno s/n, 37007 Salamanca, Spain
Interests: breast cancer; ErbB2/HER2; Neuregulin; novel therapies; epidermal growth factor receptor (EGFR)

Special Issue Information

Dear Colleagues,

Although there have been several advances in the treatment of breast cancer, for the triple-negative subtype very limited therapeutic options exist. In this breast cancer group checkpoint and PARP inhibitors have been recently incorporated into our clinical armamentarium, but there are still several challenges, such as the stratification of patients based on the right biomarkers. This Special Issue will collect a series of articles that provide new information about the current stage of novel therapeutic efforts in this indication. We will combine “up-to-date” reviews with original articles that report novel findings. We kindly encourage researchers and physician-scientists to submit their work to this Special Issue.

Prof. Alberto Ocaña
Dr. Atanasio Pandiella
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 subtype
  • PARP inhibitors
  • biomarkers
  • therapeutic approaches

Published Papers (3 papers)

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Research

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19 pages, 1507 KiB  
Article
SMARCA4 Depletion Induces Cisplatin Resistance by Activating YAP1-Mediated Epithelial-to-Mesenchymal Transition in Triple-Negative Breast Cancer
by Jihyun Kim, Gyubeom Jang, Sung Hoon Sim, In Hae Park, Kyungtae Kim and Charny Park
Cancers 2021, 13(21), 5474; https://doi.org/10.3390/cancers13215474 - 30 Oct 2021
Cited by 15 | Viewed by 3427
Abstract
The role of SMARCA4, an ATPase subunit of the SWI/SNF chromatin remodeling complex, in genomic organization is well studied in various cancer types. However, its oncogenic role and therapeutic implications are relatively unknown in triple-negative breast cancer (TNBC). We investigated the clinical [...] Read more.
The role of SMARCA4, an ATPase subunit of the SWI/SNF chromatin remodeling complex, in genomic organization is well studied in various cancer types. However, its oncogenic role and therapeutic implications are relatively unknown in triple-negative breast cancer (TNBC). We investigated the clinical implication and downstream regulation induced by SMARCA4 inactivation using large-scale genome and transcriptome profiles. Additionally, SMARCA4 was knocked out in MDA-MB-468 and MDA-MB-231 using CRISPR/Cas9 to identify gene regulation and a targetable pathway. First, we observed an increase in SMARCA4 mutations in cisplatin resistance and metastasis in TNBC patients. Its inactivation was associated with the mesenchymal-like (MSL) subtype. Gene expression analysis showed that the epithelial-to-mesenchymal transition (EMT) pathway was activated in SMARCA4-deficient patients. Next, the Hippo pathway was activated in the SMARCA4 inactivation group, as evidenced by the higher CTNNB1, TGF-β, and YAP1 oncogene signature scores. In SMARCA4 knockout cells, EMT was upregulated, and the cell line transcriptome changed from the SL to the MSL subtype. SMARCA4 knockout cells showed cisplatin resistance and Hippo-YAP/TAZ target gene activation. The YAP1 inhibitor verteporfin suppressed the expression of YAP1 target genes, and decreased cell viability and invasiveness on SMARCA4 knockout cells. SMARCA4 inactivation in TNBC endowed the resistance to cisplatin via EMT activation. The YAP1 inhibitor could become a novel strategy for patients with SMARCA4-inactivated TNBC. Full article
(This article belongs to the Special Issue Novel Targets in Triple-Negative Breast Cancer)
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14 pages, 929 KiB  
Article
Pembrolizumab Plus Gemcitabine in the Subset of Triple-Negative Advanced Breast Cancer Patients in the GEICAM/2015-04 (PANGEA-Breast) Study
by Luis de la Cruz-Merino, María Gion, Josefina Cruz-Jurado, Vanesa Quiroga, Raquel Andrés, Fernando Moreno, Jose L. Alonso-Romero, Manuel Ramos, Esther Holgado, Javier Cortés, Elena López-Miranda, Fernando Henao-Carrasco, Natalia Palazón-Carrión, Luz M. Rodríguez, Isaac Ceballos, Maribel Casas, Sara Benito, Massimo Chiesa, Susana Bezares, Rosalia Caballero, Carlos Jiménez-Cortegana, Víctor Sánchez-Margalet and Federico Rojoadd Show full author list remove Hide full author list
Cancers 2021, 13(21), 5432; https://doi.org/10.3390/cancers13215432 - 29 Oct 2021
Cited by 4 | Viewed by 2942
Abstract
The PANGEA-Breast trial evaluated a new chemo-immunotherapeutic combination that would synergistically induce long-term clinical benefit in HER2-negative advanced breast cancer patients. Treatment consisted of 21-day cycles of 200 mg of pembrolizumab (day 1) plus gemcitabine (days 1 and 8). The primary objective was [...] Read more.
The PANGEA-Breast trial evaluated a new chemo-immunotherapeutic combination that would synergistically induce long-term clinical benefit in HER2-negative advanced breast cancer patients. Treatment consisted of 21-day cycles of 200 mg of pembrolizumab (day 1) plus gemcitabine (days 1 and 8). The primary objective was the objective response rate (ORR). The tumor infiltrating lymphocytes (TILs) density and PD-L1 expression in tumor, and the myeloid-derived suppressor cells (MDSCs) level in peripheral blood, were analyzed to explore associations with treatment efficacy. Considering a two-stage Simon’s design, the study recruitment was stopped after its first stage as statistical assumptions were not met. A subset of 21 triple-negative breast cancer (TNBC) patients was enrolled. Their median age was 49 years; 15 patients had visceral involvement, and 16 had ≤3 metastatic locations. Treatment discontinuation due to progressive disease (PD) was reported in 16 patients. ORR was 15% (95% CI 3.2–37.9). Four patients were on treatment >6 months before PD. Grade ≥3 treatment-related adverse events were observed in 8 patients, where neutropenia was the most common. No association was found between TILs density, PD-L1 expression or MDSCs levels and treatment efficacy. ORR in TNBC patients also did not meet the assumptions, but 20% were on treatment >6 months. Full article
(This article belongs to the Special Issue Novel Targets in Triple-Negative Breast Cancer)
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Review

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18 pages, 511 KiB  
Review
Clinical Implications of Androgen-Positive Triple-Negative Breast Cancer
by Maša Brumec, Monika Sobočan, Iztok Takač and Darja Arko
Cancers 2021, 13(7), 1642; https://doi.org/10.3390/cancers13071642 - 01 Apr 2021
Cited by 20 | Viewed by 3280
Abstract
This review summarizes the recent findings of a vast array of studies conducted on androgen receptor-positive triple-negative breast cancer (AR-positive TNBC) to provide a better understanding of this specific breast cancer subgroup. AR expression is correlated with higher age, lower histological grade, lower [...] Read more.
This review summarizes the recent findings of a vast array of studies conducted on androgen receptor-positive triple-negative breast cancer (AR-positive TNBC) to provide a better understanding of this specific breast cancer subgroup. AR expression is correlated with higher age, lower histological grade, lower proliferation index Ki-67, spiculated masses, and calcifications on mammography. Studies investigating the correlation between AR expression and lymph node metastasis are highly discordant. In addition, results regarding prognosis are highly contradictory. AR antagonists are a promising novel therapeutic approach in AR-positive TNBC. However, AR signaling pathways should be more investigated in order to understand the influence of AR expression on TNBC more thoroughly. Full article
(This article belongs to the Special Issue Novel Targets in Triple-Negative Breast Cancer)
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