Submit to Special Issue Submit Abstract to Special Issue Review for IJMS Propose a Special Issue

Journal Menu

Journal Browser

Molecular Mechanisms and New Therapies for Breast Cancer

Special Issue Editors
Special Issue Information
Keywords
Published Papers

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 30 May 2024 | Viewed by 5457

Share This Special Issue

Special Issue Editors

Dr. Mary Lou Cutler

E-Mail Website
Guest Editor

Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA
Interests: cancer biology molecular and cell biology

Dr. Geeta Upadhyay

E-Mail Website
Guest Editor

Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA
Interests: cancer immune escape; targeted therapies; TGFbeta signaling; breast cancer; pancreatic cancer; antibodies; small molecules; CART therapies
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The goal of this special issue is to summarize new knowledge in breast cancer signaling and their implication in developing new therpeutics. There has been significant development in managing breast cancer and metastatic progression in the last decade. This special issue will focus on the review of recent clinical trial data which indicates the effectiveness of chemotherapy combinations with immunotherapies. We will entertain manuscripts focused on addressesing the challenges in bringing new biomarkers from benchside to bedside. This special issue will address the concerns of breast cancer patient advocates on current practices of breast cancer treatments. Overall, the special issue will serve as a common platform for basic scientists, bioinformaticians, statisticians and surgical oncologists to discuss the recent advances in new breast cancer therpeies which can promote an agenda for key research needs in this area for next 5–10 years.

All article research submissions should involve research at the molecular level as well as well-found verified experiments. Clinical trials and animal and cell testings are eligible only if they are strongly needed to support hypotheses or theories concerning structure–function correlations and are not suitable if no molecular aspects are considered.

Dr. Mary Lou Cutler
Dr. Geeta Upadhyay
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. 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

management of metastatic disease
neoadjuvant therapy
chemotherapy and immunotherapy combination
novel biologics
aromatase inhibitors
outcome research
quality of life during and after breast cancer therapy
new targets for TNBC

Published Papers (5 papers)

Download All Papers

Research

Jump to: Review

16 pages, 3652 KiB

Open AccessArticle

Exploring CDKN1A Upregulation Mechanisms: Insights into Cell Cycle Arrest Induced by NC2603 Curcumin Analog in MCF-7 Breast Cancer Cells

by Felipe Garcia Nishimura, Beatriz Borsani Sampaio, Tatiana Takahasi Komoto, Wanessa Julia da Silva, Mariana Mezencio Gregório da Costa, Gabriela Inforçatti Haddad, Kamila Chagas Peronni, Adriane Feijó Evangelista, Mohammad Hossain, Jonathan R. Dimmock, Brian Bandy, Rene Oliveira Beleboni, Mozart Marins and Ana Lucia Fachin

Int. J. Mol. Sci. 2024, 25(9), 4989; https://doi.org/10.3390/ijms25094989 - 03 May 2024

Viewed by 207

Abstract

Breast cancer stands out as one of the most prevalent malignancies worldwide, necessitating a nuanced understanding of its molecular underpinnings for effective treatment. Hormone receptors in breast cancer cells substantially influence treatment strategies, dictating therapeutic approaches in clinical settings, serving as a guide for drug development, and aiming to enhance treatment specificity and efficacy. Natural compounds, such as curcumin, offer a diverse array of chemical structures with promising therapeutic potential. Despite curcumin’s benefits, challenges like poor solubility and rapid metabolism have spurred the exploration of analogs. Here, we evaluated the efficacy of the curcumin analog NC2603 to induce cell cycle arrest in MCF-7 breast cancer cells and explored its molecular mechanisms. Our findings reveal potent inhibition of cell viability (IC50 = 5.6 μM) and greater specificity than doxorubicin toward MCF-7 vs. non-cancer HaCaT cells. Transcriptome analysis identified 12,055 modulated genes, most notably upregulation of GADD45A and downregulation of ESR1, implicating CDKN1A-mediated regulation of proliferation and cell cycle genes. We hypothesize that the curcumin analog by inducing GADD45A expression and repressing ESR1, triggers the expression of CDKN1A, which in turn downregulates the expression of many important genes of proliferation and the cell cycle. These insights advance our understanding of curcumin analogs’ therapeutic potential, highlighting not just their role in treatment, but also the molecular pathways involved in their activity toward breast cancer cells. Full article

(This article belongs to the Special Issue Molecular Mechanisms and New Therapies for Breast Cancer)

► Show Figures

Figure 1

15 pages, 18133 KiB

Open AccessArticle

Combination Therapy with a TLR7 Agonist and a BRD4 Inhibitor Suppresses Tumor Growth via Enhanced Immunomodulation

by Yong-Si Liu, Jia-Xin Wang, Guang-Yi Jin, Ming-Hao Hu and Xiao-Dong Wang

Int. J. Mol. Sci. 2024, 25(1), 663; https://doi.org/10.3390/ijms25010663 - 04 Jan 2024

Viewed by 1061

Abstract

JQ-1 is a typical BRD4 inhibitor with the ability to directly fight tumor cells and evoke antitumor immunity via reducing the expression of PD-L1. However, problems arise with the development of JQ-1 in clinical trials, such as marked lymphoid and hematopoietic toxicity, leading to the investigation of combination therapy. SZU-101 is a TLR7 agonist designed and synthesized by our group with potent immunostimulatory activity. Therefore, we hypothesized that combination therapy of SZU-101 and JQ-1 would target innate immunity and adaptive immunity simultaneously, to achieve a better antitumor efficacy than monotherapy. In this study, the repressive effects of the combination administration on tumor growth and metastasis were demonstrated in both murine breast cancer and melanoma models. In 4T1 tumor-bearing mice, i.t. treatment with SZU-101 in combination with i.p. treatment with JQ-1 suppressed the growth of tumors at both injected and uninjected sites. Combination therapy increased M1/M2 ratio in TAMs, decreased PD-L1 expression and promoted the recruitment of activated CD8⁺ T cells in the TME. In summary, the improved therapeutic efficacy of the novel combination therapy appears to be feasible for the treatment of a diversity of cancers. Full article

(This article belongs to the Special Issue Molecular Mechanisms and New Therapies for Breast Cancer)

► Show Figures

Figure 1

20 pages, 46677 KiB

Open AccessArticle

Therapeutic Peptide RF16 Derived from CXCL8 Inhibits MDA-MB-231 Cell Invasion and Metastasis

by Chun-Ming Chang, Chun-Chun Chang, Ho Yin Pekkle Lam, Shih-Yi Peng, Yi-Hsuan Lai, Bi-Da Hsiang, Yu-Yi Liao, Hao-Jen Hsu and Shinn-Jong Jiang

Int. J. Mol. Sci. 2023, 24(18), 14029; https://doi.org/10.3390/ijms241814029 - 13 Sep 2023

Cited by 1 | Viewed by 1086

Abstract

Interleukin (IL)-8 plays a vital role in regulating inflammation and breast cancer formation by activating CXCR1/2. We previously designed an antagonist peptide, (RF16), to inhibits the activation of downstream signaling pathways by competing with IL-8 in binding to CXCR1/2, thereby inhibiting IL-8-induced chemoattractant monocyte binding. To evaluate the effect of the RF16 peptide on breast cancer progression, triple-negative MDA-MB-231 and ER-positive MCF-7 breast cancer cells were used to investigate whether RF16 can inhibit the IL-8-induced breast cancer metastasis. Using growth, proliferation, and invasiveness assays, the results revealed that RF16 reduced cell proliferation, migration, and invasiveness in MDA-MB-231 cells. The RF16 peptide also regulated the protein and mRNA expressions of epithelial–mesenchymal transition (EMT) markers in IL-8-stimulated MDA-MB-231 cells. It also inhibited downstream IL-8 signaling and the IL-8-induced inflammatory response via the mitogen-activated protein kinase (MAPK) and Phosphoinositide 3-kinase (PI3K) pathways. In the xenograft tumor mouse model, RF16 synergistically reinforces the antitumor efficacy of docetaxel by improving mouse survival and retarding tumor growth. Our results indicate that RF16 significantly inhibited IL-8-stimulated cell growth, migration, and invasion in MDA-MB-231 breast cancer cells by blocking the activation of p38 and AKT cascades. It indicated that the RF16 peptide may serve as a new supplementary drug for breast cancer. Full article

(This article belongs to the Special Issue Molecular Mechanisms and New Therapies for Breast Cancer)

► Show Figures

Figure 1

0 pages, 1657 KiB

Open AccessArticle

Survivin Expression in Luminal Breast Cancer and Adjacent Normal Tissue for Immuno-Oncology Applications

by Sharon Wright, Scott R. Burkholz, Cathy Zelinsky, Connor Wittman, Richard T. Carback, Paul E. Harris, Tikoes Blankenberg, Charles V. Herst and Reid M. Rubsamen

Int. J. Mol. Sci. 2023, 24(14), 11827; https://doi.org/10.3390/ijms241411827 - 23 Jul 2023

Cited by 1 | Viewed by 1307

Abstract

Survivin (BIRC5) is a tumor-associated antigen (TAA) overexpressed in various tumors but present at low to undetectable levels in normal tissue. Survivin is known to have a high expression in breast cancer (e.g., Ductal Carcinoma in situ (DCIS) and triple negative breast cancer). Previous studies have not compared survivin expression levels in DCIS tumor samples to levels in adjacent, normal breast tissue from the same patient. To ensure the effective use of survivin as a target for T cell immunotherapy of breast cancer, it is essential to ascertain the varying levels of survivin expression between DCIS tumor tissue samples and the adjacent normal breast tissue taken from the same patient simultaneously. Next-generation sequencing of RNA (RNA-seq) in normal breast tissue and tumor breast tissue from five women presenting with DCIS for lumpectomy was used to identify sequence variation and expression levels of survivin. The identity of both tumor and adjacent normal tissue samples were corroborated by histopathology. Survivin was overexpressed in human breast tissue tumor samples relative to the corresponding adjacent human normal breast tissue. Wild-type survivin transcripts were the predominant species identified in all tumor tissue sequenced. This study demonstrates upregulated expression of wild type survivin in DCIS tumor tissue versus normal breast tissue taken from the same patient at the same time, and provides evidence that developing selective cytotoxic T lymphocyte (CTL) immunotherapy for DCIS targeting survivin warrants further study. Full article

(This article belongs to the Special Issue Molecular Mechanisms and New Therapies for Breast Cancer)

► Show Figures

Figure 1

Review

Jump to: Research

20 pages, 1811 KiB

Open AccessReview

Therapeutic Potential of 1,8-Dihydroanthraquinone Derivatives for Breast Cancer

by Estera Okon, Katarzyna Gaweł-Bęben, Agata Jarzab, Wojciech Koch, Wirginia Kukula-Koch and Anna Wawruszak

Int. J. Mol. Sci. 2023, 24(21), 15789; https://doi.org/10.3390/ijms242115789 - 31 Oct 2023

Viewed by 1043

Abstract

Breast cancer (BC) is the most common malignancy among women worldwide. In recent years, significant progress has been made in BC therapy. However, serious side effects resulting from the use of standard chemotherapeutic drugs, as well as the phenomenon of multidrug resistance (MDR), limit the effectiveness of approved therapies. Advanced research in the BC area is necessary to create more effective and safer forms of therapy to improve the outlook for individuals diagnosed with this aggressive neoplasm. For decades, plants and natural products with anticancer properties have been successfully utilized in treating various medical conditions. Anthraquinone derivatives are tricyclic secondary metabolites of natural origin that have been identified in plants, lichens, and fungi. They represent a few botanical families, e.g., Rhamnaceae, Rubiaceae, Fabaceae, Polygonaceae, and others. The review comprehensively covers and analyzes the most recent advances in the anticancer activity of 1,8-dihydroanthraquinone derivatives (emodin, aloe-emodin, hypericin, chrysophanol, rhein, and physcion) applied both individually, or in combination with other chemotherapeutic agents, in in vitro and in vivo BC models. The application of nanoparticles for in vitro and in vivo evidence in the context of 1,8-dihydroanthraquinone derivatives was also described. Full article

(This article belongs to the Special Issue Molecular Mechanisms and New Therapies for Breast Cancer)

► Show Figures