Molecular Insights on Signaling Cascades in Breast Cancer: A Comprehensive Review

Cancers, Journal Year: 2025, Volume and Issue: 17(2), P. 234 - 234

Published: Jan. 13, 2025

The complex signaling network within the breast tumor microenvironment is crucial for its growth, metastasis, angiogenesis, therapy escape, stem cell maintenance, and immunomodulation. An array of secretory factors their receptors activate downstream cascades regulating cancer progression metastasis. Among various pathways, EGFR, ER, Notch, Hedgehog pathways have recently been identified as in terms proliferation, survival, differentiation, maintenance CSCs, failure. These mediate such MAPK, including MEK/ERK that promote common pro-oncogenic signaling, whereas dysregulation PI3K/Akt, Wnt/β-catenin, JAK/STAT activates key oncogenic events drug resistance, CSC enrichment, metabolic reprogramming. Additionally, these orchestrate an intricate interplay between stromal cells, immune cells. Metabolic reprogramming adaptations contribute to aggressive are unresponsive therapy. Herein, recent insights into novel operating TME aid advancement emphasized current developments practices targeting enhance treatment efficacy reviewed.

Language: Английский

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CDKN2A^Lowcancer cells outcompete macrophages for microenvironmental zinc to drive immunotherapy resistance

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 8, 2025

ABSTRACT Approximately 50% of cancers exhibit decreased CDKN2A expression ( Low ), which is linked to immune checkpoint blockade (ICB) resistance. While traditionally recognized as a tumor suppressor and cell cycle regulator, we have previously put forth new paradigm demonstrating its role in intracellular metabolic reprogramming. Whether the derangement due loss alters metabolites within microenvironment (TME) how that affects compartment ICB response has never been investigated. Here found cancer cells reorganize zinc compartmentalization by upregulating importer SLC39A9 plasma membrane, leading accumulation concurrent depletion TME. This competition for results zinc-starved macrophages, reduced phagocytic activity. Remarkably, restoring levels TME through dietary intervention re-educates macrophages pro-phagocytic phenotype, sensitizing tumors ICB. Unexpectedly, T are not required this response. Clinically, from patients signatures, corresponding phagocytosis signatures. Moreover, with low circulating time-to-event outcomes compared those higher levels. Our work reveals unrecognized mechanism outcompete zinc, directly disrupting their function efficacy.

Language: Английский

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Tumor associated macrophages in breast cancer progression: implications and clinical relevance

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: July 9, 2024

Macrophages represent an immune cell population characterized by high plasticity and a range of properties functions. Their activation status specific phenotype are highly associated with their localization the environmental cues they receive. The roles macrophages in cancer development diverse. Despite antitumor effects at early stages disease, presence tumor microenvironment (TME) has been linked to promotion upon disease establishment. Tumor (TAMs) key components breast TME have poor clinical outcomes. High TAM densities were found correlate progression, increased metastatic potential prognosis. Interestingly, considerably higher levels TAMs patients triple negative (TNBC)—the most aggressive type cancer—compared other types. present review summarizes recent findings regarding distinct subsets involvement progression metastasis. It highlights constant interplay between cells its major contribution including such aspects as, polarization toward promoting phenotype, induction epithelial mesenchymal transition (EMT) enhancement stem properties. Further, we discuss relevance these findings, focusing on how better delineation metastasis will facilitate selection more efficient treatment options.

Language: Английский

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Chemotherapy induces myeloid-driven spatially confined T cell exhaustion in ovarian cancer

Cancer Cell, Journal Year: 2024, Volume and Issue: 42(12), P. 2045 - 2063.e10

Published: Dec. 1, 2024

Language: Английский

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Pan-Cancer Analysis of KANK2: Clinical and Molecular Insights into Tumor Progression and Therapeutic Implications

Journal of Cancer, Journal Year: 2025, Volume and Issue: 16(4), P. 1149 - 1166

Published: Jan. 6, 2025

KANK2, a gene crucial for cell migration and movement, is implicated in neoplastic non-neoplastic diseases. This study aimed to analyze KANK2's expression its diagnostic prognostic significance across 33 cancers using multiple online databases. comprehensively KANK2 The Cancer Genome Atlas (TCGA) Genotype-Tissue Expression (GTEx) database. Multiple web platforms software were used data analysis, including R, Cytoscape, HPA, TISIDB, UALCAN, GEO, cBioPortal, STRING, GSCALite, CancerSEA. WB qPCR experiments verify the results. widely expressed various tissues has significant value cancers, with AUC values exceeding 0.75 13 cancer types. Survival analysis indicated that significantly associated overall survival (OS) disease-specific (DSS) several cancers. varied different molecular immune subtypes was specific genetic mutations DNA methylation patterns. Functional state highlighted correlations processes such as EMT, angiogenesis, apoptosis. GSEA identified pathways related proliferation, migration, extracellular matrix remodeling. key interacting proteins by PPI network sensitive drug molecules found GSCA results also confirmed two GEO datasets serves valuable biomarker diagnosis prognosis intricately linked cellular processes, offering potential therapeutic targets future research.

Language: Английский

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Gene mutation, clinical characteristics and pathology in resectable lung adenocarcinoma

World Journal of Surgical Oncology, Journal Year: 2025, Volume and Issue: 23(1)

Published: Jan. 22, 2025

With the wide use of CT scan in clinical practice, more lung cancer was diagnosed resectable stage. Pathological examination and genetic testing have become a routine procedure for adenocarcinoma following radical resection. This study analyzed special pathological components gene mutations to explore their relationship with characteristics overall survival. Clinical, pathological, mutation data from 1,118 patients were collected. All underwent surgery at Department Thoracic Surgery, Second Xiangya Hospital Central South University. Patients grouped based on mutations. Differences features survival as well. mucinous, neuroendocrine, poor-differentiated presented prognostic risk factors, including pleural invasion, carcinothrombosis, STAS, advanced stages, along varying frequencies These factors significantly shortened ALK KRAS also associated such solid nodules, later stages. However, significant reduction observed only mutation. Relationship between still requires further investigation. Special (mucinous, poor-differentiated) had an influence biological behavior tumors, resulting different prognosis.

Language: Английский

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Nanobody-based drug delivery systems for cancer therapy

Journal of Controlled Release, Journal Year: 2025, Volume and Issue: 381, P. 113562 - 113562

Published: Feb. 22, 2025

Language: Английский

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Analysis of single-cell and spatial transcriptomics in TNBC cell-cell interactions

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 26, 2025

Triple-negative breast cancer (TNBC) is a highly malignant tumor in women, characterized by high morbidity, mortality, and recurrence rates. Although surgical treatment, radiotherapy, chemotherapy are the mainstays of current treatment methods, heterogeneity TNBC results unsatisfactory outcomes with low 5-year survival Rapid advancements omics technology have propelled understanding molecular biology. The emergence single-cell RNA sequencing (scRNA-seq) spatial transcriptomics (ST) has significantly enhanced knowledge distribution, functionality, intercellular interactions various cell types within microenvironment, including cells, T B macrophages, fibroblasts. present study provides an overview technical characteristics scRNA-seq ST, highlighting their applications exploring heterogeneity, distribution patterns, interactions. This review aims to enhance comprehension at cellular level for development effective therapeutic targets.

Language: Английский

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Myeloid cells: key players in tumor microenvironments

Frontiers of Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: March 6, 2025

Language: Английский

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New insights into cancer immune checkpoints landscape from single-cell RNA sequencing

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2025, Volume and Issue: 1880(3), P. 189298 - 189298

Published: March 13, 2025

Language: Английский

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