The breast differentiation antigen NY-BR-1: A novel target antigen for active immunotherapy in breast cancer

: Immunotherapy emerges as a treatment strategy for breast cancer marker, diagnosis and treatment. In this review, monoclonal antibodies (mAbs)-based passive and peptide vaccines as active immunotherapy approaches like activation of B-cells and T-cells are studied. Passive immunotherapy is mAbs-based therapy effective against tumor cells, which acts by targeting HER2, IGF 1R, VEGF, BCSC and immune checkpoints. Neuropeptide Y (NPY) and GPCR are the areas of interest to target BC metastases for on-targeting therapeutic action. Neuropeptide S (NPS) or NPS receptor 1, acts as a biomarker for Neuroendocrine tumors (NET), mostly characterized by synaptophysin and chromogranin-A expression or Ki-67 proliferation index. The protein fusion technologies arise as a promising avenue in plant expression systems for increased recombinant Ab accumulation and cost-efficient purification. Recently, mAbs-based immunotherapy effectiveness is appreciated as a novel therapeutic combination of chemotherapy and immunotherapy to reduce the side effects and improve therapeutic responsiveness. Synthetic drug resistance will be overcome by mAbs-based therapy through several clinical trials and detection methods need to be optimized for accuracy and precision. Pharmacokinetic attributes need to be accessed for preferred receptor-agonist activity without ligand accumulation.

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Exploring a Novel Target Treatment on Breast Cancer: Aloe-emodin Mediated Photodynamic Therapy Induced Cell Apoptosis and Inhibited Cell Metastasis

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520615666150821093323 ◽

2016 ◽

Vol 16 (6) ◽

pp. 763-770 ◽

Cited By ~ 11

Author(s):

Qing Chen ◽

Si Tian ◽

Jing Zhu ◽

Kai-Ting Li ◽

Ting-He Yu ◽

...

Keyword(s):

Breast Cancer ◽

Photodynamic Therapy ◽

Cell Apoptosis ◽

Cell Metastasis ◽

Target Treatment ◽

Aloe Emodin ◽

Novel Target

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Metabotropic glutamate receptor 1 is associated with unfavorable prognosis in ER-negative and triple-negative breast cancer

Scientific Reports ◽

10.1038/s41598-020-79248-4 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Anna E. M. Bastiaansen ◽

A. Mieke Timmermans ◽

Marcel Smid ◽

Carolien H. M. van Deurzen ◽

Esther S. P. Hulsenboom ◽

...

Keyword(s):

Breast Cancer ◽

Protein Expression ◽

Glutamate Receptor ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Metabotropic Glutamate Receptor ◽

Metabotropic Glutamate ◽

Metabotropic Glutamate Receptor 1 ◽

Novel Target ◽

Cancer Tissues

AbstractNew therapies are an urgent medical need in all breast cancer subgroups. Metabotropic glutamate receptor 1 (mGluR1) is suggested as a potential new molecular target. We examined the prevalence mGluR1 expression in different clinically relevant breast cancer subgroups and determined its association with prognosis. In this retrospective cohort, 394 consecutive primary breast cancer tissues were incorporated into a tissue microarray and immunohistochemically stained for mGluR1. The prevalence of mGluR1 protein expression in different breast cancer subgroups was evaluated and correlated with metastasis-free survival (MFS) and overall survival (OS). In total, 56% (n = 219) breast cancer tissues had mGluR1 expression. In estrogen receptor (ER)-negative tumors, 31% (n = 18/58) had mGluR1 expression that was significantly associated with MFS (HR 5.00, 95% CI 1.03–24.35, p = 0.046) in multivariate analysis, independently from other prognostic factors. Of the 44 triple-negative breast cancer (TNBC), 25% (n = 11) expressed mGluR1. mGluR1 expression in TNBC was significantly associated with shorter MFS (HR 8.60, 95% CI 1.06–20.39, p = 0.044) and with poor OS (HR 16.07, 95% CI 1.16–223.10, p = 0.039). In conclusion, mGluR1 is frequently expressed in breast cancer. In ER-negative breast cancer and in TNBC mGluR1 protein expression is an unfavorable prognostic marker. This study provides rationale to explore mGluR1 as a novel target for breast cancer treatment, especially for the more aggressive TNBC.

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Antibody–Drug Conjugates for the Treatment of Breast Cancer

Cancers ◽

10.3390/cancers13122898 ◽

2021 ◽

Vol 13 (12) ◽

pp. 2898

Author(s):

Chiara Corti ◽

Federica Giugliano ◽

Eleonora Nicolò ◽

Liliana Ascione ◽

Giuseppe Curigliano

Keyword(s):

Breast Cancer ◽

Bystander Effect ◽

Metastatic Breast ◽

Therapeutic Index ◽

Cytotoxic Agents ◽

Target Antigen ◽

Her2 Positive ◽

Antibody Drug Conjugates ◽

Drug Conjugates ◽

Antibody Drug

Metastatic breast cancer (BC) is currently an incurable disease. Besides endocrine therapy and targeted agents, chemotherapy is often used in the treatment of this disease. However, lack of tumor specificity and toxicity associated with dose exposure limit the manageability of cytotoxic agents. Antibody–drug conjugates (ADCs) are a relatively new class of anticancer drugs. By merging the selectivity of monoclonal antibodies with the cytotoxic properties of chemotherapy, they improve the therapeutic index of antineoplastic agents. Three core components characterize ADCs: the antibody, directed to a target antigen; the payload, typically a cytotoxic agent; a linker, connecting the antibody to the payload. The most studied target antigen is HER2 with some agents, such as trastuzumab deruxtecan, showing activity not only in HER2-positive, but also in HER2-low BC patients, possibly due to a bystander effect. This property to provide a cytotoxic impact also against off-target cancer cells may overcome the intratumoral heterogeneity of some target antigens. Other cancer-associated antigens represent a strategy for the development of ADCs against triple-negative BC, as shown by the recent approval of sacituzumab govitecan. In this review, we discuss the current landscape of ADC development for the treatment of BC, as well as the possible limitations of this treatment.

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Oncogenic UBE3C promotes breast cancer progression by activating Wnt/β-catenin signaling

Cancer Cell International ◽

10.1186/s12935-020-01733-7 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Chen Hang ◽

Shanojie Zhao ◽

Tiejun Wang ◽

Yan Zhang

Keyword(s):

Breast Cancer ◽

Cancer Progression ◽

Nuclear Accumulation ◽

Migration And Invasion ◽

Ubiquitin Protein Ligase ◽

Novel Target ◽

First Time ◽

Breast Tissues

Abstract Background Breast cancer (BrCa) is the most common female malignancy worldwide and has the highest morbidity among all cancers in females. Unfortunately, the mechanisms of BrCa growth and metastasis, which lead to a poor prognosis in BrCa patients, have not been well characterized. Methods Immunohistochemistry (IHC) was performed on a BrCa tissue microarray (TMA) containing 80 samples to evaluate ubiquitin protein ligase E3C (UBE3C) expression. In addition, a series of cellular experiments were conducted to reveal the role of UBE3C in BrCa. Results In this research, we identified UBE3C as an oncogenic factor in BrCa growth and metastasis for the first time. UBE3C expression was upregulated in BrCa tissues compared with adjacent breast tissues. BrCa patients with high nuclear UBE3C expression in tumors showed remarkably worse overall survival (OS) than those with low nuclear expression. Knockdown of UBE3C expression in MCF-7 and MDA-MB-453 BrCa cells inhibited cell proliferation, migration and invasion in vitro, while overexpression of UBE3C in these cells exerted the opposite effects. Moreover, UBE3C promoted β-catenin nuclear accumulation, leading to the activation of the Wnt/β-catenin signaling pathway in BrCa cells. Conclusion Collectively, these results imply that UBE3C plays crucial roles in BrCa development and progression and that UBE3C may be a novel target for the prevention and treatment of BrCa.

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MicroRNA let-7g directly targets forkhead box C2 (FOXC2) to modulate bone metastasis in breast cancer

Open Medicine ◽

10.1515/med-2017-0023 ◽

2017 ◽

Vol 12 (1) ◽

pp. 157-162 ◽

Cited By ~ 3

Author(s):

Lei Wang ◽

Ming Li ◽

Yongxin Zhou ◽

Yu Zhao

Keyword(s):

Breast Cancer ◽

Cell Migration ◽

Bone Metastasis ◽

Western Blot ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Qrt Pcr ◽

Forkhead Box ◽

Novel Target ◽

Cancer Tissues

AbstractAberrantly expressed microRNAs have been implicated in lots of cancers. Reduced amounts of let-7g have been found in breast cancer tissues. The function of let-7g in bone metastasis of breast cancer remains poorly understood. This study is to explore the significance of let-7g and its novel target gene in bone metastasis of breast cancer.The expression of let-7g or forkhead box C2 (FOXC2) was measured in human clinical breast cancer tissues with bone metastasis by using quantitative real-time Polymerase Chain Reaction (qRT-PCR). After transfection with let-7g or anti-let-7g in breast cancer cell linesMDA-MB-231or SK-BR3, qRT-PCR and Western blot were done to test the levels of let-7g and FOXC2. The effect of anti-let-7g and/ or FOXC2 RNA interference (RNAi) on cell migration in breast cancer cells was evaluated by using wound healing assay.Clinically, qRT-PCR showed that FOXC2 levels were higher in breast cancer tissues with bone metastasis than those in their noncancerous counterparts. Let-7g was showed to be negatively correlated with FOXC2 in human breast cancer samples with bone metastasis. We found that enforced expression of let-7g reduced levels of FOXC2 protein by using Western blot in MDA-MB-231 cells. Conversely, anti-let-7g enhanced levels of FOXC2 in SK-BR3 cells. In terms of function, anti-let-7g accelerated migration of SK-BR3 cells. Interestingly, FOXC2 RNAi abrogated anti-let-7g-mediated migration in breast cancer cells. Thus, we conclude that let-7g suppresses cell migration through targeting FOXC2 in breast cancer. Our finding provides a new perspective for understanding the mechanism of bone metastasis in breast cancer.

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CENP-O, a Protein Localized at the Centromere Throughout the Cell Cycle, Is a Novel Target Antigen in Systemic Sclerosis

The Journal of Rheumatology ◽

10.3899/jrheum.080726 ◽

2009 ◽

Vol 36 (4) ◽

pp. 781-786 ◽

Cited By ~ 10

Author(s):

AKIKO SAITO ◽

YOSHINAO MURO ◽

KAZUMITSU SUGIURA ◽

MASASHI IKENO ◽

KINYA YODA ◽

...

Keyword(s):

Cell Cycle ◽

Western Blotting ◽

High Reactivity ◽

Antigenic Structure ◽

Target Antigen ◽

Cell Extracts ◽

Systemic Autoimmunity ◽

Minor Population ◽

Anticentromere Antibodies ◽

Novel Target

Objective.CENP-A, -B, and -C are major centromere components and the main targets of anticentromere antibodies (ACA). Many other proteins are also assembled around CENP-A nucleosomes in interphase nuclei to form the interphase centromere complex (ICEN). The CENP-O protein is a component of the ICEN that localizes at the centromere throughout the cell cycle. We investigated whether CENP-O is also targeted by sera from patients with systemic autoimmune diseases.Methods.Sera from 114 patients with ACA and 142 patients without ACA were analyzed. Western blotting and an ELISA with bacterially expressed recombinant CENP-O protein were performed to screen for the presence of anti-CENP-O antibodies. In addition, anti-CENP-O antibody-positive sera were tested by Western blotting HeLa cell extracts to examine reactivity with the major centromere antigens.Results.Four female patients with ACA had anti-CENP-O antibodies. There was no correlation of anti-CENP-O antibodies with specific clinical features or other serological features. However, one of the 4 patients, who showed a unique clinical course of scleroderma, had sera with markedly high reactivity to CENP-O.Conclusion.CENP-O protein is a novel centromere antigen that is recognized by a very minor population of ACA-positive patients with scleroderma. Because CENP-O is an ICEN component, ICEN may be a large antigenic structure in systemic autoimmunity.

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MicroRNA-1246 Suppresses the Metastasis of Breast Cancer Cells by Targeting the DRAK1A/PGRN Axis to Prevent the Epithelial-Mesenchymal Transition

10.21203/rs.3.rs-516130/v1 ◽

2021 ◽

Author(s):

Pan Wang ◽

Wenju Chen ◽

Yaqiong Zhang ◽

Qianyi Zhong ◽

Zhaoyun Li ◽

...

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Breast Cancer Cells ◽

Triple Negative ◽

Epithelial Mesenchymal Transition ◽

Migration And Invasion ◽

Mesenchymal Transition ◽

Tnbc Cell ◽

Novel Target

Abstract Objective. Breast cancer is one of the most common malignant and highly heterogeneous tumors in women. MicroRNAs (miRNAs), such as miR-1246, play important roles in various types of malignant cancers, including triple-negative breast cancer (TNBC). However, the biological role of miR-1246 in TNBC has not yet been fully elucidated. In this study, we studied the role of miR-1246 in the occurrence and development of TNBC and its mechanism of action.Methods. Cell Counting Kit-8 (CCK-8), wound healing, and Transwell assays were performed to observe the effects of miR-1246 on TNBC cell proliferation, migration, and invasion, respectively. The expression of epithelial-mesenchymal transition (EMT) markers was detected by western blotting. Dual luciferase reporter assays were performed to determine whether DYRK1A is a novel target of miR-1246. In addition, an immunoprecipitation experiment was performed to verify the binding of DYRK1A to PGRN. Rescue experiments were performed to determine whether DYRK1A is a novel target of miR-1246 and whether miR-1246 suppresses the metastasis of breast cancer cells by targeting the DRAK1A/PGRN axis to prevent the epithelial-mesenchymal transition.Results. Our results show that miR‑1246 suppresses the proliferation, migration, and invasion of TNBC cells and that DYRK1A is a novel target of miR-1246. MiR‑1246 plays a suppressive role in the regulation of the EMT of TNBC cells by targeting DYRK1A. DYRK1A mediates the metastasis of triple-negative breast cancer via activation of the EMT. We identified PGRN as a novel DYRK1A-interacting protein. DYRK1A and PGRN act together to regulate the occurrence and development of breast cancer through miR-1246.Conclusion. miR-1246 attenuates TNBC cell invasion and the EMT by targeting the DRAK1A/PGRN axis. Our data suggest that miR‑1246 may be used to develop novel early-stage diagnostic and therapeutic strategies for TNBC.

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