Single-cell RNA sequencing reveals cell heterogeneity and transcriptome profile of breast cancer lymph node metastasis

Oncogenesis, Journal Year: 2021, Volume and Issue: 10(10)

Published: Oct. 5, 2021

Abstract Molecular mechanisms underlying breast cancer lymph node metastasis remain unclear. Using single-cell sequencing, we investigated the transcriptome profile of 96,796 single cells from 15 paired samples primary tumors and axillary nodes. We identified nine cell subclusters including CD44 + / ALDH2 /ALDH6A1 stem (BCSCs), which had a copy-number variants similar to that normal tissue. Importantly, BCSCs existed only in evolved into metastatic clusters infiltrating Furthermore, data suggested NECTIN2-TIGIT-mediated interactions between tumor microenvironment (TME) cells, promoted immune escape metastasis. This study is first delineate using RNA sequencing. Our findings offer novel insights have implications developing therapies inhibit initiation

Language: Английский

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Therapeutic progress and challenges for triple negative breast cancer: targeted therapy and immunotherapy

Molecular Biomedicine, Journal Year: 2022, Volume and Issue: 3(1)

Published: March 4, 2022

Abstract Triple negative breast cancer (TNBC) is a subtype of cancer, with estrogen receptor, human epidermal growth factor receptor 2 and progesterone negative. TNBC characterized by high heterogeneity, rates metastasis, poor prognosis, lack therapeutic targets. Now the treatment still based on surgery chemotherapy, which effective only in initial stage but almost useless advanced stage. And due to hormone target, hormonal therapies have little beneficial effects. In recent years, signaling pathways receptor-specific targets been reported be patients under specific clinical conditions. targeted approved for many other cancers even subtypes options are limited. Most showed no response, may related heterogeneity TNBC, therefore more treatments predictive biomarkers needed. present review, we summarize potential opinions dysregulated receptors pathways, play significant role multiple stages development. We also focus application immunotherapy preclinical trials therapy TNBC. hope accelerate research development new drugs understanding relevant mechanisms, improve survival.

Language: Английский

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Tailored therapies for triple-negative breast cancer: current landscape and future perceptions

Naunyn-Schmiedeberg s Archives of Pharmacology, Journal Year: 2025, Volume and Issue: unknown

Published: March 3, 2025

Language: Английский

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Breast cancer immunotherapy: Current and novel approaches

International Immunopharmacology, Journal Year: 2021, Volume and Issue: 98, P. 107886 - 107886

Published: June 19, 2021

Language: Английский

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TNBC: Potential Targeting of Multiple Receptors for a Therapeutic Breakthrough, Nanomedicine, and Immunotherapy

Biomedicines, Journal Year: 2021, Volume and Issue: 9(8), P. 876 - 876

Published: July 23, 2021

Triple-negative breast cancer (TNBC) is a heterogeneous, recurring associated with high rate of metastasis, poor prognosis, and lack therapeutic targets. Although target-based options are approved for other cancers, only limited available TNBC. Cell signaling receptor-specific targets reportedly effective in patients TNBC under specific clinical conditions. However, most these cancers unresponsive, there requirement more treatment modalities. Further, biomarkers that can distinguish from BC subtypes. ER, PR, HER2 help identify widely used to who likely respond diverse strategies. In this review, we discuss the possible based on its inherent subtype receptors pathways, such as p53 signaling, AKT cell cycle regulation, DNA damage, programmed death, which play essential roles at multiple stages development. We focus poly-ADP ribose polymerase 1, androgen receptor, vascular endothelial growth factor epidermal receptor well application nanomedicine immunotherapy their potential applications drug development

Language: Английский

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PRMT5 reduces immunotherapy efficacy in triple-negative breast cancer by methylating KEAP1 and inhibiting ferroptosis

Journal for ImmunoTherapy of Cancer, Journal Year: 2023, Volume and Issue: 11(6), P. e006890 - e006890

Published: June 1, 2023

As an emerging treatment strategy for triple-negative breast cancer (TNBC), immunotherapy acts in part by inducing ferroptosis. Recent studies have shown that protein arginine methyltransferase 5 (PRMT5) has distinct roles among multiple cancers modulating the tumor microenvironment. However, role of PRMT5 during ferroptosis, especially TNBC immunotherapy, is unclear.PRMT5 expression was measured IHC (immunohistochemistry) staining. To explore function ferroptosis inducers and functional experiments were conducted. A panel biochemical assays used to discover potential mechanisms.PRMT5 promoted resistance but impaired non-TNBC. Mechanistically, selectively methylated KEAP1 thereby downregulated NRF2 its downstream targets which can be divided into two groups: pro-ferroptosis anti-ferroptosis. We found cellular ferrous level might a critical factor determining cell fate as changes. In context higher concentrations cells, inhibited NRF2/HMOX1 pathway slowed import ferrous. addition, high indicated strong inhibitors potentiated therapeutic efficacy immunotherapy.Our results reveal activation modulate iron metabolism drive immunotherapy. Accordingly, target change immune TNBC.

Language: Английский

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Cancer Vaccines for Triple-Negative Breast Cancer: A Systematic Review

Vaccines, Journal Year: 2023, Volume and Issue: 11(1), P. 146 - 146

Published: Jan. 9, 2023

Triple-negative breast cancer (TNBC) is the subtype of with poorest outcomes, and associated a high risk relapse metastasis. The treatment choices for this malignancy have been confined to conventional chemotherapeutic agents, due lack expression canonical molecular targets. Immunotherapy has recently changing paradigm many types tumors, approach evoking active immune responses in milieu tumors through vaccines introduced as one most novel immunotherapeutic approaches. Accordingly, number or prevention recurrence developed are currently being studied TNBC patients, while none yet received any approvals. To elucidate efficacy safety these vaccines, we performed systematic review available literature on topic. After searching PubMed, Scopus, Web Science, Embase, Cochrane CENTRAL, Google Scholar databases, total 5701 results were obtained, from which 42 clinical studies eventually included based predefined criteria. overall quality was acceptable. However, reporting outcomes survival progression some (which presented conference abstracts) well heterogeneity reported study designs, not able carry out meta-analysis. A 32 different so far evaluated majority belonging peptide-based vaccine type. other cell nucleic acid (RNA/DNA)-based categories. Most proved be safe low-grade, local adverse events could efficiently evoke cellular responses; however, trials demonstrate significant improvements indices efficacy. This part limited randomized studies, population each trial. encouraging published trials, anticipate that strategy show its potential larger, phase III near future.

Language: Английский

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Classifications of triple-negative breast cancer: insights and current therapeutic approaches

Cell & Bioscience, Journal Year: 2025, Volume and Issue: 15(1)

Published: Feb. 1, 2025

Triple-negative breast cancer (TNBC) is an aggressive and challenging type of cancer, characterized by the absence specific receptors targeted current therapies, which limits effective treatment options. TNBC has a high risk recurrence distant metastasis, resulting in lower survival rates. Additionally, exhibits significant heterogeneity at histopathological, proteomic, transcriptomic, genomic levels, further complicating development treatments. While some subtypes may initially respond to chemotherapy, resistance frequently develops, increasing recurrence. Therefore, precisely classifying characterizing distinct features crucial for identifying most suitable molecular-based therapies individual patients. In this review, we provide comprehensive overview these subtypes, highlighting their unique profiles as defined various classification systems. We also address limitations conventional therapeutic approaches explore innovative biological strategies, all aimed advancing strategies TNBC.

Language: Английский

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A Systematic Review on the Therapeutic Potentiality of PD-L1-Inhibiting MicroRNAs for Triple-Negative Breast Cancer: Toward Single-Cell Sequencing-Guided Biomimetic Delivery

Genes, Journal Year: 2021, Volume and Issue: 12(8), P. 1206 - 1206

Published: Aug. 4, 2021

The programmed death-ligand 1 (PD-L1)/programmed cell death protein (PD-1) is a well-established inhibitory immune checkpoint axis in triple-negative breast cancer (TNBC). Growing evidence indicates that tumoral PD-L1 can lead to TNBC development. Although conventional inhibitors have improved patients' prognosis, their effect mainly focused on improving anti-tumoral responses without substantially regulating oncogenic signaling pathways cells. Moreover, the cannot impede de novo expression of oncoproteins, like PD-L1, Accumulating has indicated restoration specific microRNAs (miRs) downregulate and inhibit Since miRs target multiple mRNAs, miR-based gene therapy be an appealing approach restore responses, regulate various intracellular singling TNBC. Therefore, we conducted current systematic review based preferred reporting items for reviews meta-analyses (PRISMA) provide comprehensive unbiased synthesis currently available regarding PD-L1-inhibiting development tumor microenvironment. For this purpose, systematically searched Cochrane Library, Embase, Scopus, PubMed, ProQuest, Web Science, Ovid, IranDoc databases obtain relevant peer-reviewed studies published before 25 May 2021. Based evidence, miR-424-5p, miR-138-5p, miR-570-3p, miR-200c-3p, miR-383-5p, miR-34a-5p, miR-3609, miR-195-5p, miR-497-5p expression, transform immunosuppressive microenvironment into pro-inflammatory microenvironment, proliferation, suppress migration, enhance chemosensitivity cells, stimulate apoptosis, arrest cycle, repress clonogenicity Concerning biocompatibility biomimetic carriers valuable insights provided by single-cell sequencing technologies, sequencing-guided delivery these decrease toxicity traditional approaches, increase specificity miR-delivery, efficacy miR delivery, affected patients with personalized therapy.

Language: Английский

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Tumor-targeted self-assembled micelles reducing PD-L1 expression combined with ICIs to enhance chemo-immunotherapy of TNBC

Chinese Chemical Letters, Journal Year: 2023, Volume and Issue: 35(2), P. 108536 - 108536

Published: May 6, 2023

Language: Английский

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