Who’s Who? Discrimination of Human Breast Cancer Cell Lines by Raman and FTIR Microspectroscopy DOI Open Access
Inês Santos, Clara B. Martins, Luís A. E. Batista de Carvalho

et al.

Cancers, Journal Year: 2022, Volume and Issue: 14(2), P. 452 - 452

Published: Jan. 17, 2022

(1) Breast cancer is presently the leading cause of death in women worldwide. This study aims at identifying molecular biomarkers human breast cells, order to differentiate highly aggressive triple-negative from non-triple-negative cancers, as well distinct subtypes, which currently an unmet clinical need paramount for improved patient care. (2) Raman and FTIR (Fourier transform infrared) microspectroscopy state-of-the-art techniques were applied, sensitive, specific non-invasive methods probing heterogeneous biological samples such cells. (3) Particular biochemical features malignancy unveiled based on cells' vibrational signature, upon principal component analysis data. enabled discrimination between TNBC (triple-negative cancer) non-TNBC, MSL (mesenchymal stem cell-like) BL1 (basal-like 1) metastatic low-metastatic cell lines. differentiation subtypes-mesenchymal basal-like, basal-like 1 with high-metastatic potential potential-is a pioneer result, high impact diagnosis treatment.

Language: Английский

Tumor-associated macrophages promote epithelial–mesenchymal transition and the cancer stem cell properties in triple-negative breast cancer through CCL2/AKT/β-catenin signaling DOI Creative Commons

Xiangzhou Chen,

Mingqiang Yang,

Jiang Yin

et al.

Cell Communication and Signaling, Journal Year: 2022, Volume and Issue: 20(1)

Published: June 17, 2022

Triple-negative breast cancer (TNBC) is a highly aggressive subtype of with poor prognosis and limited treatment. As major component the tumor microenvironment, tumor-associated macrophages (TAMs) play an important role in facilitating behavior TNBC. This study aimed to explore novel mechanism TAMs regulation epithelial-mesenchymal transition (EMT) stem cell (CSC) properties TNBC.Expression M2-like macrophage marker CD163 was evaluated by immunohistochemistry human tissues. The phenotype M2 polarized from Tohoku-Hospital-Pediatrics-1 (THP1) cells verified flow cytometry. Transwell assays, wound healing western blotting, cytometry, ELISA, quantitative polymerase chain reaction (qPCR), luciferase reporter gene immunofluorescence assays were conducted investigate which regulate EMT CSC BT549 HCC1937 cells.Clinically, we observed high infiltration TNBC tissues confirmed that associated unfavorable patients. Moreover, found conditioned medium (M2-CM) markedly promoted cells. Mechanistically, demonstrated chemokine (C-C motif) ligand 2 (CCL2) secretion activated Akt signaling, turn increased expression nuclear localization β-catenin. Furthermore, β-catenin knockdown reversed TAM-induced properties.This provides promote enhance via activation CCL2/AKT/β-catenin may offer new strategies for diagnosis treatment Video Abstract.

Language: Английский

Citations

85
A review of biological targets and therapeutic approaches in the management of triple-negative breast cancer DOI Creative Commons
Hitesh Kumar, Neha Gupta, Rupshee Jain

et al.

Journal of Advanced Research, Journal Year: 2023, Volume and Issue: 54, P. 271 - 292

Published: Feb. 14, 2023

Triple-negative breast cancer (TNBC) is a heterogeneous, aggressive phenotype of with associated chemoresistance. The development chemo- or radioresistance could be attributed to diverse tumor microenvironments, overexpression membrane proteins (transporters), epigenetic changes, and alteration the cell signaling pathways/genes stem cells (CSCs). Due heterogeneous nature TNBC, therapeutic response existing modalities offers limited scope thus results in reccurance after therapy. To establish landmark efficacy, number novel have been proposed. In addition, reversal resistance that developed during treatment may altered by employing appropriate modalities. This review aims discuss plethora investigations carried out, which will help readers understand make an choice therapy directed toward complete elimination TNBC. manuscript addresses major contributory factors from microenvironment are responsible for chemoresistance poor prognosis. cellular events molecular mechanism-based interventions explained detail. Inhibition ABC transporters, pathways CSCs, modification promising this regard. TNBC progression, invasion, metastasis recurrence can also inhibited blocking multiple pathways, targeting specific receptors/epigenetic targets, disrupting bioenergetics generating reactive oxygen species (ROS).

Language: Английский

Citations

59
Implantable Microneedles Loaded with Nanoparticles Surface Engineered Escherichia coli for Efficient Eradication of Triple-Negative Breast Cancer Stem Cells DOI
Weinan Zhang,

Yechun Jiang,

Litao Liu

et al.

Nano Letters, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 21, 2025

Eliminating cancer stem cells (CSCs) is essential for the effective treatment of triple-negative breast (TNBC). This study synthesized Au@cerium-zinc composite core@shell nanoparticles (Au@Zn/CeO) that were subsequently conjugated with Escherichia coli (E. coli) to create engineered bacterium AZCE, which was then combined microneedle carriers and freeze-dried obtain AZCE-MN. Upon implantation into TNBC tumors, inherent properties E. facilitate AZCE penetrate extracellular matrix break through basement membrane, enabling delivery AZC CSCs-enriched regions deep within tumor. The released Zn2+ induces mitochondrial dysfunction amplifies reactive oxygen species (ROS) production. redox cycling between Ce3+/Ce4+ effectively depleted glutathione, further increased ROS generation. Under near-infrared laser irradiation, Au nanorods initiated photothermal therapy, ablating CSCs while amplifying catalytic reactions ionic effects. microneedle-mediated bacteria improved nanodrug penetration in tumor tissues, providing new insights clinical treatment.

Language: Английский

Citations

3
Tailored therapies for triple-negative breast cancer: current landscape and future perceptions DOI

Yumna Khan,

Sana Rizvi, Ali Raza

et al.

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

Published: March 3, 2025

Language: Английский

Citations

2
The CLIP1–LTK fusion is an oncogenic driver in non‐small‐cell lung cancer DOI
Hiroki Izumi, Shingo Matsumoto, Jie Liu

et al.

Nature, Journal Year: 2021, Volume and Issue: 600(7888), P. 319 - 323

Published: Nov. 24, 2021

Language: Английский

Citations

58
Challenges and Opportunities in Developing Targeted Therapies for Triple Negative Breast Cancer DOI Creative Commons

Abygail G. Chapdelaine,

Gongqin Sun

Biomolecules, Journal Year: 2023, Volume and Issue: 13(8), P. 1207 - 1207

Published: Aug. 1, 2023

Triple negative breast cancer (TNBC) is a heterogeneous group of cancers characterized by their lack estrogen receptors, progesterone and the HER2 receptor. They are more aggressive than other subtypes, with higher mean tumor size, grade, worst five-year overall survival, highest rates recurrence metastasis. Developing targeted therapies for TNBC has been major challenge due to its heterogeneity, treatment still largely relies on surgery, radiation therapy, chemotherapy. In this review article, we efforts in developing TNBC, discuss insights gained from these efforts, highlight potential opportunities going forward. Accumulating evidence supports TNBCs as multi-driver cancers, which multiple oncogenic drivers promote cell proliferation survival. such would require drug combinations that simultaneously block drivers. A strategy designed generate mechanism-based combination discussed.

Language: Английский

Citations

23
Epigenetic modulations in triple-negative breast cancer: Therapeutic implications for tumor microenvironment DOI Creative Commons
Linlin Zhou, Danny Yu

Pharmacological Research, Journal Year: 2024, Volume and Issue: 204, P. 107205 - 107205

Published: May 6, 2024

Triple-negative breast cancer (TNBC) is an aggressive subtype lacking estrogen receptors, progesterone receptors and lacks HER2 overexpression. This absence of critical molecular targets poses significant challenges for conventional therapies. Immunotherapy, remarkably immune checkpoint blockade, offers promise TNBC treatment, but its efficacy remains limited. Epigenetic dysregulation, including altered DNA methylation, histone modifications, imbalances in regulators such as BET proteins, plays a crucial role development resistance to treatment. Hypermethylation tumor suppressor gene promoters the imbalance methyltransferases EZH2 deacetylases (HDACs) profoundly influence cell proliferation, survival, metastasis. In addition, epigenetic alterations critically shape microenvironment (TME), composition, cytokine signaling, expression, ultimately contributing evasion. Targeting these mechanisms with specific inhibitors HDAC combination immunotherapy represents compelling strategy remodel TME, potentially overcoming evasion enhancing therapeutic outcomes TNBC. review aims comprehensively elucidate current understanding modulation TNBC, on potential combining therapies overcome posed by this subtype.

Language: Английский

Citations

15
Overcoming doxorubicin resistance in triple-negative breast cancer using the class I-targeting HDAC inhibitor bocodepsin/OKI-179 to promote apoptosis DOI Creative Commons

Stephen G. Smoots,

Anna Schreiber,

Marilyn M Jackson

et al.

Breast Cancer Research, Journal Year: 2024, Volume and Issue: 26(1)

Published: March 1, 2024

Abstract Background Triple-negative breast cancer (TNBC) is an aggressive subtype with a poor prognosis. Doxorubicin part of standard curative therapy for TNBC, but chemotherapy resistance remains important clinical challenge. Bocodepsin (OKI-179) small molecule class I histone deacetylase (HDAC) inhibitor that promotes apoptosis in TNBC preclinical models. The purpose this study was to investigate the combination bocodepsin and doxorubicin models evaluate impact on terminal cell fate, including senescence. Methods lines were treated CellTiter-Glo used assess proliferation determine sensitivity. Select OKI-005 (in vitro version bocodepsin) assessed proliferation, as measured by Annexin V/PI, cycle flow cytometry. Immunoblotting changes mediators apoptosis, arrest, Senescence senescence-associated β-galactosidase assay. An MDA-MB-231 xenograft vivo model bocodepsin, doxorubicin, or inhibition tumor growth. shRNA knockdown p53 performed CAL-51 line senescence response treatment. Results resulted synergistic antiproliferative activity cells regardless mutation status. led increased decreased In vivo, growth compared either single agent. knock-down doxorubicin-induced addition vitro. Conclusion vitro, improved promotion which makes promising overcome TNBC. currently development has favorable toxicity profile other HDAC inhibitors supporting feasibility evaluating patients

Language: Английский

Citations

9
DNA methylation and immune evasion in triple-negative breast cancer: challenges and therapeutic opportunities DOI Creative Commons

Wenyu Cai,

Xiaoli Cai,

Yi-ran Fei

et al.

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

Citations

1
HDAC Inhibitors for the Therapy of Triple Negative Breast Cancer DOI Creative Commons
Cristina Maccallini, Alessandra Ammazzalorso, Barbara De Filippis

et al.

Pharmaceuticals, Journal Year: 2022, Volume and Issue: 15(6), P. 667 - 667

Published: May 26, 2022

Triple negative breast cancer (TNBC) is an urgent as well huge medical challenge, which associated with poor prognosis and responsiveness to chemotherapies. Since epigenetic changes are highly implicated in TNBC tumorigenesis development, inhibitors of histone deacetylases (HDACIs) could represent a promising therapeutic strategy. Although clinical trials involving single HDACIs showed disappointing results against TNBC, recent studies emphasize the high potential impact controlling TNBC. In addition, encouraging stem from new compounds designed obtain isoform selectivity and/or polypharmacological HDAC approach. The present review provides discussion pharmacophoric models structural modifications, leading potent activity progression.

Language: Английский

Citations

33