Genetic Heterogeneity, Tumor Microenvironment and Immunotherapy in Triple-Negative Breast Cancer

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(23), P. 14937 - 14937

Published: Nov. 29, 2022

Heterogeneity of triple-negative breast cancer is well known at clinical, histopathological, and molecular levels. Genomic instability greater mutation rates, which may result in the creation neoantigens enhanced immunogenicity, are additional characteristics this type. Clinical outcome poor due to early age onset, high metastatic potential, increased likelihood distant recurrence. Consequently, efforts elucidate mechanisms development, progression, spread have been initiated improve treatment options outcomes for these patients. The extremely complex heterogeneous tumor immune microenvironment made up several cell types commonly possesses disorganized gene expression. Altered signaling pathways mainly associated with mutated genes including p53, PIK3CA, MAPK, positively correlated regulating response. Of note, particular immunity-associated could be used prognostic indexes assess most effective management. Recent findings highlight fact that long non-coding RNAs also play an important role shaping formation, can mediate evasion. Identification signatures, through use multi-omics approaches, effector drive stages carcinogenic process steps developing new strategies targeted prevention. Advances immunotherapy by remodeling host system eradicate cells great promise lead novel therapeutic strategies. Current research focused on combining checkpoint inhibition chemotherapy, PARP inhibitors, vaccines, or natural killer therapy. Targeted therapies response, eliminate resistance, overall patient survival. In future, evolving advancements should implemented personalized medicine state-of-art management

Language: Английский

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DNA methylation and immune evasion in triple-negative breast cancer: challenges and therapeutic opportunities

Frontiers in Oncology, Journal Year: 2025, Volume and Issue: 15

Published: Feb. 6, 2025

Triple-negative breast cancer (TNBC) is an aggressive subtype of characterized by the lack estrogen receptor (ER), progesterone (PR), and human epidermal growth factor 2 (HER2). Chemotherapy remains primary treatment option, yet TNBC frequently develops resistance, leading to relapse metastasis. Emerging evidence highlights potential combining DNA methylation inhibitors with immune checkpoint (ICIs). contributes escape silencing immune-regulatory genes, thereby reducing tumor's visibility cells. Reversing this epigenetic modification can reinvigorate surveillance enhance efficacy immunotherapies. This review discusses role in progression evasion, focusing on recent advances combination therapies involving ICIs. We discuss underlying mechanisms that enable these therapeutic synergies, preclinical clinical supporting approach, challenges posed tumor heterogeneity, drug toxicity. Finally, we explore for personalized strategies incorporating multi-omics data optimize outcomes. The integration immunotherapy offers a promising avenue improving survival patients.

Language: Английский

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Overcoming anti-PD-1/PD-L1 immune checkpoint blockade resistance: the role of macrophage, neutrophils and mast cells in the tumor microenvironment

Clinical and Experimental Medicine, Journal Year: 2023, Volume and Issue: 23(7), P. 3077 - 3091

Published: April 6, 2023

Language: Английский

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Aberrant promoter hypermethylation of miR-335 and miR-145 is involved in breast cancer PD-L1 overexpression

Scientific Reports, Journal Year: 2023, Volume and Issue: 13(1)

Published: Jan. 18, 2023

Abstract PD-L1 is one of the most important immune checkpoint molecules in breast cancer that plays an role suppressing system when confronted with tumor cells and regulated by various microRNAs. Among them, microRNA-335-3p microRNA-145-5p, DNA methylation, have suppressor activities. We studied miR-335 -145 on suppression cancer. The expression miR-355 miR-145 was significantly downregulated BC tissues cell lines compared to their controls, downregulation negatively correlated PD‐L1 overexpression. In-silico luciferase reporter systems confirmed target PD-L1. In lines, cancer-specific methylation found CpG-rich areas upstream and-145, up-regulation connected hypermethylation (r = 0.4089, P 0.0147, r 0.3373, 0.0475, respectively). higher levels induced apoptosis, arrested cycle, reduced proliferation significantly. summary, we are novel suppressors inactivated BC, these miRs may serve as potential therapeutic targets for treatment.

Language: Английский

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Roles and mechanisms of miR-195–5p in human solid cancers

Biomedicine & Pharmacotherapy, Journal Year: 2022, Volume and Issue: 150, P. 112885 - 112885

Published: April 19, 2022

Cancer persists as a worldwide disease that contributes to high morbidity and mortality rates. As class of non-coding RNA, microRNAs (miRNAs) are one kind important regulators in cancer frequently implicated tumor development progression. Emerging experiments have suggested miRNA-195–5p (miR-195–5p) can regulate neoplastic processes many pathways. For instance, miR-195–5p not only proliferation, migration invasion cells but also promote cell apoptosis. Furthermore, low expression could induce drug resistance. Our review focuses on the various tumors elucidates related mechanisms which participates biology, well summarizes roles We believe might potential utility novel diagnostic biomarker therapeutic target for cancer.

Language: Английский

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New Achievements for the Treatment of Triple-Negative Breast Cancer

Applied Sciences, Journal Year: 2022, Volume and Issue: 12(11), P. 5554 - 5554

Published: May 30, 2022

Triple-negative breast cancer (TNBC) constitutes a heterogeneous group of malignancies that are often aggressive and associated with poor prognosis. The development new TNBC treatment strategies has become an urgent clinical need. Diagnosis subtyping essential to establish alternative treatments targeted therapies for every patient. Chemotherapy, particularly anthracycline taxanes, remains the backbone medical management both early metastatic TNBC. More recently, immune checkpoint inhibitors therapy have revolutionized treatment. Included in different studied is drug repurposing. Despite numerous medications available, studies medicinal chemistry still aimed at synthesis compounds order find antiproliferative agents capable treating Additionally, some supplemental micronutrients, nutraceuticals functional foods can potentially reduce risk developing or retard rate growth metastases established malignant diseases. Finally, nanotechnology medicine, termed nanomedicines, introduces nanoparticles variable architecture This review highlights most recent search TNBC, along repositioning drugs.

Language: Английский

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Decoding the Intricate Landscape of Pancreatic Cancer: Insights into Tumor Biology, Microenvironment, and Therapeutic Interventions

Cancers, Journal Year: 2024, Volume and Issue: 16(13), P. 2438 - 2438

Published: July 2, 2024

Pancreatic ductal adenocarcinoma (PDAC) presents significant oncological challenges due to its aggressive nature and poor prognosis. The tumor microenvironment (TME) plays a critical role in progression treatment resistance. Non-neoplastic cells, such as cancer-associated fibroblasts (CAFs) tumor-associated macrophages (TAMs), contribute growth, angiogenesis, immune evasion. Although cells infiltrate TME, evade responses by secreting chemokines expressing checkpoint inhibitors (ICIs). Vascular components, like endothelial pericytes, stimulate angiogenesis support while adipocytes secrete factors that promote cell invasion, Additionally, perineural characteristic feature of PDAC, contributes local recurrence Moreover, key signaling pathways including Kirsten rat sarcoma viral oncogene (KRAS), transforming growth factor beta (TGF-β), Notch, hypoxia-inducible (HIF), Wnt/β-catenin drive Targeting the TME is crucial for developing effective therapies, strategies inhibiting CAFs, modulating response, disrupting blocking neural interactions. A recent multi-omic approach has identified signature genes associated with anoikis resistance, which could serve prognostic biomarkers targets personalized therapy.

Language: Английский

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p53 downregulates PD-L1 expression via miR-34a to inhibit the growth of triple-negative breast cancer cells: a potential clinical immunotherapeutic target

Molecular Biology Reports, Journal Year: 2022, Volume and Issue: 50(1), P. 577 - 587

Published: Nov. 9, 2022

Language: Английский

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MicroRNAs with Multiple Targets of Immune Checkpoints, as a Potential Sensitizer for Immune Checkpoint Inhibitors in Breast Cancer Treatment

Cancers, Journal Year: 2023, Volume and Issue: 15(3), P. 824 - 824

Published: Jan. 29, 2023

Breast cancer is the most common type and leading cause of cancer-associated mortality in women worldwide. In recent years, immune checkpoint inhibitors (ICIs) have made significant progress treatment breast cancer, yet there are still a considerable number patients who unable to gain lasting ideal clinical benefits by immunotherapy alone, which leads development combination regimen as novel research hotspot. Furthermore, one miRNA can target several molecules, mimicking therapeutic effect combined blockade (ICB), means that therapy has been considered increase efficiency ICIs. this review, we summarized potential therapeutics candidates affect multiple targets checkpoints with more potential, obstacles applying therapeutically through analyses resources available from drug perspective. We also included content “too many for effect” (TMTME), TargetScan database, discuss adverse events. This review aims ignite enthusiasm explore application miRNAs ICIs treating cancer.

Language: Английский

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A scoping review on the potentiality of PD-L1-inhibiting microRNAs in treating colorectal cancer: Toward single-cell sequencing-guided biocompatible-based delivery

Biomedicine & Pharmacotherapy, Journal Year: 2021, Volume and Issue: 143, P. 112213 - 112213

Published: Sept. 22, 2021

Tumoral programmed cell death ligand 1 (PD-L1) has been implicated in the immune evasion and development of colorectal cancer. Although monoclonal checkpoint inhibitors can exclusively improve prognosis patients with microsatellite instability-high (MSI-H) tumor mutational burden-high (TMB-H) cancer, specific tumor-suppressive microRNAs (miRs) regulate multiple oncogenic pathways inhibit de novo expression oncoproteins, like PD-L1, both stable (MSS) MSI-H cancer cells. This scoping review aimed to discuss currently available evidence regarding therapeutic potentiality PD-L1-inhibiting miRs for For this purpose, Web Science, Scopus, PubMed databases were systematically searched obtain peer-reviewed studies published before 17 March 2021. We have found that miR-191–5p, miR-382–3p, miR-148a-3p, miR‐93–5p, miR-200a-3p, miR-200c-3p, miR-138–5p, miR-140–3p, miR-15b-5p tumoral PD-L1 Besides inhibiting substantially reduce migration, development, stimulate anti-tumoral responses, decrease viability, enhance chemosensitivity cells regardless state. Concerning specific, effective, safe delivery these miRs, single-cell sequencing-guided biocompatible-based increase specificity miR delivery, toxicity traditional nanoparticles, transform immunosuppressive microenvironment into proinflammatory one, suppress

Language: Английский

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