Seminars in Cancer Biology, Journal Year: 2025, Volume and Issue: unknown
Published: Jan. 1, 2025
Language: Английский
Frontiers in Molecular Biosciences, Journal Year: 2022, Volume and Issue: 9
Published: Aug. 19, 2022
Triple-negative breast cancer (TNBC) is a clinically aggressive subtype of that represents 15-20% tumors and more prevalent in young pre-menopausal women. It the cancers with highest metastatic potential recurrence at first 5 years after diagnosis. In addition, mortality increases when complete pathological response not achieved. As TNBC cells lack estrogen, progesterone, HER2 receptors, patients do respond well to hormone anti-HER2 therapies, conventional chemotherapy remains standard treatment. Despite efforts develop targeted this disease continues have high unmet medical need, there an urgent demand for customized diagnosis therapeutics. immunotherapy changing paradigm anticancer treatment, it arises as alternative treatment patients. classified immunogenic due its levels tumor mutational burden presence immune cell infiltrates. This review addresses implications these characteristics diagnosis, prognosis disease. Herein, role gene signatures tumor-infiltrating lymphocytes biomarkers reviewed, identifying their application patient stratification, predictors efficacy. The expression PD-L1 already considered be predictive checkpoint inhibitor therapy, but challenges regarding value biomarker are described. Moreover, rationales different formats against currently under clinical research discussed, major trials highlighted. Immune inhibitors demonstrated benefit, particularly early-stage administered combination chemotherapy, several regimens approved by regulatory authorities. success antibody-drug conjugates on other emerging approaches, such vaccines will also addressed. These advances give hope development personalized, effective, safe treatments, which improve survival quality life TNBC.
Language: Английский
Citations
36
BioMed Research International, Journal Year: 2022, Volume and Issue: 2022, P. 1 - 13
Published: July 6, 2022
Despite being more aggressive than other types of breast cancer, there is no suitable treatment for triple-negative cancer (TNBC). Here, we designed doxorubicin-containing solid lipid nanoparticles (SLNs) decorated with anti-EGFR/CD44 dual-RNA aptamers, which are overexpressed in TNBC. For efficiency the nuclear delivery doxorubicin, dexamethasone (Dexa) was chemically attached to surface nanoparticles.To prepare cationic SLNs, 6-lauroxyhexyl BOC-ornithine (LHON) synthesized and form Dexa-LHON complexes. The SLNs were prepared via double emulsification (w/o/w) solvent evaporation technique. preparation statistically optimized using central composite response methodology. Independent factors GMS/lecithin concentration ratio amount Tween 80, while responses considered particle size, polydispersity index, entrapment nanoparticles. studied morphologically transmission electron microscopy, vitro release doxorubicin from phosphate-buffered saline. Then, designated aptamers electrostatic interactions, their cytotoxicity assessed vitro.The PDI, zeta potential, EE%, LE% 101 ± 12.6 nm, 0.341 0.005, +13.6 1.83 mV, 69.98 7.54%, 10.2 1.06%, respectively. TEM images revealed spherical sign aggregation. In study exhibited that 96.1 1.97% released within 48 h incubation. attachment nanoparticles' confirmed by reducing potential -15.6 2.07 mV. experiments SLNs/DOX/Dexa/CD44 or EGFR substantially successful SLNs/DOX/Dexa at inhibiting cell proliferation. Using MDA-MB-468 line, discovered SLN/DOX/Dexa/CD44/EGFR effective constructs proliferation (p < 0.001). reduction viability this construct suggests targeting numerous pathways effective.Overall, finding investigation suggested SLNs/DOX/Dexa/CD44/EGFR could be a promising new enhanced anticancer system deserved further preclinical consideration.
Language: Английский
Citations
29
Bioactive Materials, Journal Year: 2023, Volume and Issue: 33, P. 483 - 496
Published: Dec. 3, 2023
Limited by low tumor immunogenicity and the immunosuppressive microenvironment (TME), triple-negative breast cancer (TNBC) has been poorly responsive to immunotherapy so far. Herein, a Ca & Mn dual-ion hybrid nanostimulator (CMS) is constructed enhance anti-tumor immunity through ferroptosis inducing innate awakening, which can serve as inducer immunoadjuvant for TNBC concurrently. On one hand, glutathione (GSH) depletion reactive oxygen species (ROS) generation be achieved due mixed valence state of in CMS. other an exotic Ca2+ supplier, CMS causes mitochondrial overload, further amplifies oxidative stress. Significantly, cells undergo because inactivation peroxidase 4 (GPX4) accumulation lipid peroxidation (LPO). More impressively, act awaken alleviating intra-tumor hypoxia Mn2+-induced activation STING signaling pathway, promotes polarization tumor-associated macrophages (TAMs) dendritic (DCs) antigen presentation subsequent infiltration tumor-specific cytotoxic T lymphocytes (CTLs) into tissues. Taken together, this work demonstrates novel strategy simultaneously awakening immunity, offering new perspective effective TNBC.
Language: Английский
Citations
19
Heliyon, Journal Year: 2024, Volume and Issue: 10(7), P. e28242 - e28242
Published: March 27, 2024
The close association between cuproptosis and tumor immunity in triple-negative breast cancer (TNBC) allows its monitoring for predicting the prognosis of patients with TNBC. Nevertheless, biological function prognostic value cuproptosis-related miRNAs their target genes have not been reported.
Language: Английский
Citations
7
ACS Applied Bio Materials, Journal Year: 2024, Volume and Issue: 7(3), P. 2012 - 2022
Published: March 7, 2024
Triple-negative breast cancer (TNBC) remains a clinical challenge due to molecular, metabolic, and genetic heterogeneity as well the lack of validated drug targets. Thus, therapies or delivery paradigms are needed. Gold-derived compounds including FDA-approved drug, auranofin have shown promise effective anticancer agents against several tumors. To improve solubility bioavailability auranofin, we hypothesized that nanodelivery using biodegradable chitosan modified polyethylene glycol (PEG) nanoparticles (NPs) will enhance activity TNBC by comparing best nanoformulation with free drug. The selection was based on synthesis various PEG copolymers via formaldehyde-mediated engraftment onto form [chitosan-g-PEG] copolymer. Furthermore, altered physiochemical properties copolymer formaldehyde ratio towards (CP 1–4 NPs). Following recruitment polymer surface, explored how this process influenced stiffness nanoparticle atomic force microscopy (AFM), factor crucial for in vitro vivo studies. Our objective ensure full functionality inherent parent maintained without allowing overshadow chitosan's unique cationic while improving neutral pH. Hence, CP 2 NP chosen. demonstrate efficacy good carrier administered dose 3 mg/kg contrast which given at 5 mg/kg. In studies revealed potency encapsulated cells severe necrotic effect following treatment superior auranofin. conclusion, chitosan-g-PEG potential be an excellent system increasing its effectiveness potentially reducing limitations.
Language: Английский
Citations
6
Discovery Medicine, Journal Year: 2024, Volume and Issue: 36(182), P. 613 - 613
Published: Jan. 1, 2024
Background: Breast cancer (BC), a common tumor in women, has high morbidity and mortality. Formononetin, an active ingredient red clover Astragalus membranaceus, wide range of pharmacological applications, including as anticancer agent. Since immunotherapy is hot topic the treatment strategy BC, it was dedicated to appraising specific mechanism formononetin BC this research. Methods: Different concentrations (0, 20, 40, 60, 80, 100 μM) were used treat cells transfected with pcDNA3.1-Programmed death ligand 1 (PD-L1) or Short-hairpin RNA (sh)-PD-L1. Cells separated into four subgroups: CTRL, pcDNA3.1-PD-L1, sh-CTRL, sh-PD-L1. Cell viability cell cycle assessed through Methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay flow cytometry. Programmed mRNA concentration validated via quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). metastasis evaluated cloning transwell assay. The p-STING/stimulator interferon genes (STING), p-p65/p65, PD-L1 determined by western blot. Results: Formononetin restrained proliferation MCF-7 MDA-MB-468 cells, reduced mRNA, p-STING/STING, p-p65/p65 protein concentrations. Whereas inhibition pcDNA3.1-PD-L1 intervention had opposite result. STING pathway inhibitor C-176 combined further proliferation, colony formation, invasion, contrast treated alone. Conclusion: can restrain which may be mediated interference suppression activation STING-NF-κB pathway.
Language: Английский
Citations
6
Advances in Cancer Biology - Metastasis, Journal Year: 2023, Volume and Issue: 7, P. 100090 - 100090
Published: Feb. 6, 2023
Breast Cancer arises to be the most diagnosed cancer type in recent decades. It ranks vulnerable among women terms of incidence and mortality. In 2020, 2.3 million were with breast cancer, 6.85 lacs death reported globally. Here, we will focus mainly on TNBC, complicated subtype. Therefore, novel treatment modalities are urgently required. Treatments like chemotherapy radiotherapy limit efficacy therapeutic outcomes. Thus, new specific ideas coming up find a way out. For triple-negative (TNBC), which is currently complex challenging subtype treat, still standard care. There has been lot study into treatments for people TNBC because its poor prognosis high chance clinical recurrence. Chimeric antigen receptor (CAR) T cell-based immunotherapy directs patient's immune system recognize eradicate tumor cells that express tumor-associated antigens (TAAs). opens area research. Antigen Receptor (CAR-T) cell therapy an derived from adoptive relocation. CAR-T well equipped antibodies identify self-tumor cells, thus bringing out cytotoxic CARs modified receptors improved specificity responsiveness intensify recognition cells. The effects treatment, including have not lived expectations solid tumors despite triumphs treating hematologic malignancies. this review, discuss some developments field cancer-specific using CAR-T.
Language: Английский
Citations
13
Current Oncology, Journal Year: 2023, Volume and Issue: 30(2), P. 2127 - 2143
Published: Feb. 9, 2023
Tumor evolution to evade immune surveillance is a hallmark of carcinogenesis, and the modulation tumor immunogenicity has been challenge present therapeutic responses in immunotherapies alone for numerous cancers. By altering cell phenotype reshaping microenvironment, epigenetic modifications enable cells overcome as mechanism cancer progression immunotherapy resistance. Demethylase enzymatic activity lysine-specific demethylase 1 (LSD1), histone first identified 2004, plays pivotal role vast cellular processes cancer. While FDA-approved indications therapies are limited hematological malignancies, it imperative understand how machinery can be targeted prime breast In this review, we discuss potential roles epigenetics demethylating agent LSD1 potent new management strategy combat current challenges cancers, which have presented modest efficacy checkpoint inhibitors till date. Additionally, describe combined use LSD1-specific existing preclinical clinical trials that elicits robust response benefit. Overall, promising results observed LSD1-targeting signify central novel resistance commonly seen immunotherapies.
Language: Английский
Citations
13
Cancer Reports, Journal Year: 2023, Volume and Issue: 6(S1)
Published: Jan. 12, 2023
Abstract In 2020, newly diagnosed breast cancer (BC) cases surpassed that of lung among women, making it the most common female globally. spite recent increases in incidence rates, mortality due to BC has declined since 1989. These declines have been attributed advancements treatment modalities as well increased mammography surveillance. Despite these advances, African American (AA) women are 40% more likely die from than Caucasian women. Multifactorial etiology implicated disparity rates AA As an example, a disproportionate triple negative (TNBC), which poor prognosis and marginal options. Increasingly, tumor microenvironment (TME) gained relevance relates primary progression, metastasis possibilities. The outcomes or pathological complete response (pCR) TNBC affected by differences TME. TME exhibit several variances acellular cellular components associated with pro‐tumorigenic effects. For levels adipocyte‐related hormone, resistin, pro‐inflammatory cytokine, IL‐6, CC chemokine, CCL2, within gives rise density M2 macrophages, also known tumor‐associated macrophages. Elevated vascular endothelial growth factor increase vascularity, facilitate aggressive metastasis. Furthermore, is supported CXC CXCL12 results recruitment regulatory T lymphocytes (T regs ). Due other precision oncology can target specific aspects may contribute poorer prognosis. addition discrepancies TME, face socio‐economic barriers limit their ability access state‐of‐the‐art, novel therapies against metastatic TNBC. this review, we will provide brief overview immune microenvironment, immune‐based options for potential decrease health disparities ethnicity.
Language: Английский
Citations
12
Scientific Reports, Journal Year: 2023, Volume and Issue: 13(1)
Published: April 11, 2023
Among the different breast cancer subsets, triple-negative (TNBC) has worst prognosis and limited options for targeted therapies. Immunotherapies are emerging as novel treatment opportunities TNBC. However, surging immune response elicited by immunotherapies to eradicate cells can select resistant cells, which may result in escape tumor evolution progression. Alternatively, maintaining equilibrium phase of be advantageous keeping a long-term presence small-size residual tumor. Myeloid-derived suppressor (MDSCs) activated, expanded, recruited microenvironment tumor-derived signals shape pro-tumorigenic micro-environment suppressing innate adaptive anti-tumor responses. We recently proposed model describing immune-mediated dormancy instigated vaccine consisting dormant, immunogenic derived from murine 4T1 TNBC-like cell line. Strikingly, these 4T1-derived dormant fewer MDSCs compared aggressive cells. Recent experimental studies demonstrated that inactivating profound impact on reconstituting surveillance against Here, we developed deterministic mathematical simulating depletion mice bearing tumors resulting immunomodulation. Our computational simulations indicate vaccination strategy with small number combination MDSC elicit an effective growth subsequent challenge sustained dormancy. The results predict therapeutic opportunity based induction immunity
Language: Английский
Citations
12