Editorial: Advances of brain metastasis in breast cancer

Frontiers in Human Neuroscience, Journal Year: 2025, Volume and Issue: 19

Published: Jan. 22, 2025

Breast cancer is the most frequently diagnosed malignancy among women worldwide and a leading cause of cancer-related deaths. Brain metastasis, severe complication advanced breast cancer, significantly worsens prognosis due to challenges posed by blood-brain barrier (BBB) aggressive nature metastatic cells (1). The development brain metastases from involves multiple steps, including detachment primary tumor, invasion into bloodstream, colonization (2). BBB, which protects harmful substances, also limits effectiveness many chemotherapeutic agents. Recent studies have identified several molecular pathways genetic mutations that facilitate penetration through BBB their subsequent growth in brain. Key players include HER2 (human epidermal factor receptor 2) BRCA (breast gene) mutations, are associated with more disease higher likelihood metastasis (3,4). This research topic aims highlight recent advances treatments discovery new targets or agents, novel methods pre-clinical clinical trials, as well deeper insights focusing on known agents treatments.Understanding basis central nervous system crucial for developing effective treatments. Lipocalin-2 (LCN2), an iron transport protein, implicated progression (BCBM) (5). In tumors, LCN2 promotes cell proliferation, angiogenesis, interacting matrix metalloproteinase-9 facilitating epithelialmesenchymal transition. microenvironment, disrupts bloodbrain aids tumor seeding modulating cellular behavior. Zhang et al. reviewed LCN2's role BCBM its potential therapeutic target biomarker, suggesting targeting could improve outcomes patients.Extracellular vesicles (EVs), small lipid bilayer containing biomolecules, play this process delivering bioactive molecules recipient regulating signal transduction protein expression. EVs were confirmed key regulation immune microenvironment expected make immunotherapy diagnosis. ( 6) Yusuke Yoshioka mechanisms promote discusses EV-associated early diagnostic markers.Immune checkpoint inhibitors (ICIs) represent promising option patients BCBM, particularly those TNBC otherwise very limited nonchemotherapy systemic therapy options (7). However, it remains essential investigate factors influencing efficacy ICIs treatment. A study found high mutation burden (TMB) lesions suggests benefits (8). Additionally, TREML2 BTLA poor prognostic factors, activated microglia may serve treatment targets. Mustafa investigated increasing incidence patients, lung cancers, despite advancements targeted therapies. It explored differences between these cancers identify specific druggable Analyzing 44 tissue samples, significant upregulation genes tumors compared metastases. findings association upregulated metabolic stress pathways, response regulation, growth, proliferation. Notably, expression checkpoints VTCN1 VISTA, IDO1, NT5E, HDAC3 adenocarcinoma validated. suggested be targets.Multiple drugs been validated trials both safe DESTINY-Breast12 (DB12) evaluated safety trastuzumab deruxtecan (T-DXd) HER2-positive median progression-free survival (PFS) was 17.3 months, 12-month PFS rate 61.6%. intracranial objective (CNS ORR) 71.7%, indicating strong treating (9). When combined capecitabine, tucatinib has improved extracranial overall after previous trastuzumab-deruxtecan (10). Ping Sun anti-angiogenic agent anlotinib triple-negative (TNBC) who had failed prior 29 October 2019 April 2024, PFS) 7.2 (OS) 10.2 months. (iORR) 31.0%, control (iDCR) 86.2%. Five experienced grade 3-4 adverse events, bone marrow suppression being common. Most events manageable, no treatment-related deaths occurred. offered metastases.In conclusion, articles compiled Research Topic offer thorough examination understanding metastasis. persist. Ongoing therapies enhancing quality life suffering devastating condition.

Language: Английский

Role of Extracellular Vesicles in the Progression of Brain Tumors

Biology, Journal Year: 2024, Volume and Issue: 13(8), P. 586 - 586

Published: Aug. 2, 2024

Brain tumors, and, in particular, glioblastoma (GBM), are among the most aggressive forms of cancer. In spite advancement available therapies, both diagnosis and treatments still unable to ensure pathology-free survival GBM patients for more than 12–15 months. At basis poor ability cope with brain we can consider: (i) intra-tumor heterogeneity; (ii) heterogeneity tumor properties when compare different patients; (iii) blood–brain barrier (BBB), which makes difficult isolation tumor-specific biomarkers delivering therapeutic drugs brain. Recently, it is becoming increasingly clear that cancer cells release large amounts extracellular vesicles (EVs) transport metabolites, proteins, classes RNAs, DNA, lipids. These structures involved pathological process characterize any particular form Moreover, EVs able cross BBB directions. Starting from these observations, researchers now evaluating possibility use purified organic fluids (first all, blood saliva), order obtain, through non-invasive methods (liquid biopsy), biomarkers, perhaps, also obtaining nanocarriers targeted drugs.

Language: Английский

Rotenone induced acute miRNA alterations in extracellular vesicles produce mitochondrial dysfunction and cell death

npj Parkinson s Disease, Journal Year: 2025, Volume and Issue: 11(1)

Published: March 27, 2025

How extracellular vesicles (EVs) may contribute to mechanisms of primary intracellular pathogenesis in Parkinson's disease (PD) remains unknown. To critically advance our understanding how EVs influence early-stage PD pathogenesis, we tested the hypothesis that rats acutely exposed neurotoxin rotenone would produce differential miRNAs CSF/serum-derived and such modulation be responsible for PD-relevant functional alterations recipient neuronal cells. We discovered acute treatment produced significant specific serum miRNA alterations. Primary midbrain neurons treated with from rotenone-exposed oxidative stress, mitochondrial toxicity, cell loss culture. These were dependent on miR-30a-5p miR-484. Thus, this study has elucidated expression circulating serum/CSF is a potential early diagnostic marker PD, cellular functions viability due determines pathological fate.

Language: Английский