Umbilical cord mesenchymal stem cell exosomes in breast cancer. False hope or a real solution?

Genetic epilepsies include a broad spectrum of disorders caused by pathogenic variants in more than 1,000 genes. Their clinical expression is highly variable, making early phenotype-genotype interpretation challenging. Early seizure semiology and EEG features may offer clinically useful information for diagnostic orientation and management. The aim of this study was to characterize early clinical and EEG features in patients with genetic epilepsies, examine their associations with outcomes, and explore genotype-phenotype groupings through hierarchical clustering analysis (HCA). We conducted a retrospective study at Bambino Gesù Children's Hospital. Eligible participants carried pathogenic or likely pathogenic variants in epilepsy-related genes, identified through medical records and laboratory diagnostic logs. Clinical variables at seizure onset and EEG recordings performed within the first month of the initial seizure were extracted. Follow-up outcomes included seizure frequency, drug resistance, movement disorders, behavioral/autism spectrum disorder comorbidities, and developmental delay/intellectual disability (DD/ID). Associations between early features and outcomes were assessed using χ2 or Fisher tests. HCA was used to identify clusters linking early phenotype and gene-level etiology. We included 277 patients (52.3% female; median age at last follow-up 8.1 years, range 0-40). Drug resistance occurred in 58.8% and severe DD/ID in 35.4% of patients. EEG data at onset were available for 107 individuals. Neonatal onset was associated with a higher rate of drug resistance (71.4%; odds ratio [OR] 2.0, 95% CI 1.05-3.77), movement disorders (60.7%; OR 3.7, 95% CI 2.02-6.82), and severe DD/ID (71.4%; OR 7.0, 95% CI 3.66-13.49). Slow EEG background activity and multifocal epileptiform discharges were associated with both drug resistance and severe DD/ID. HCA identified genotype-phenotype groupings, including clusters involving SCN1A, PRRT2, STXBP1, KCNQ2, SCN2A, CHD2, SYNGAP1, and MECP2, each linked to specific clinical and EEG features. Early clinical and EEG features showed meaningful associations with outcomes and mapped onto specific genetic etiologies. HCA revealed coherent genotype-phenotype clusters that may support early diagnostic reasoning. Limitations include the retrospective design and small numbers per gene, warranting larger multicenter studies for validation.

Altered residence time as a cause of drug resistance.

Cancer cell metastasis and drug resistance: Unravelling the role of NF-κB and cyclin D1 pathways and their crosstalk.

The role of the microbiota in cancer drug resistance and emerging therapeutic strategies.

Lenvatinib-resistant liver cancer-derived HSP90α-containing extracellular vesicles enhance drug resistance via macrophage CXCL8 secretion.

Phytogalactolipids triggered oxidative stress to inhibit drug-resistant colorectal cancer by suppressing interferon-α-induced protein 6.

Pharmacological activation of cGAS-STING pathway to reverse cancer drug resistance.

Encapsulation of hydroxyurea in exosomes derived from adipose mesenchymal stem cells enhances anticancer efficacy in breast cancer.

Βreast cancer (BC) is the most common malignant tumor among women. Its significant heterogeneity and complex molecular mechanisms pose major clinical challenges, including limited therapeutic efficacy and drug resistance. Recently, microRNAs (miRs) have been recognized as key post‑transcriptional regulators involved in tumorigenesis and tumor progression through multiple pathways. Among these, the miR‑200 family (miR‑200a, miR‑200b, miR‑200c, miR‑429 and miR‑141) has attracted considerable attention due to its pivotal role in BC. The present review systematically summarizes the genomic characteristics, expression regulation mechanisms and biological functions of the miR‑200 family in BC. Special emphasis is given to their roles in epithelial‑mesenchymal transition, cell proliferation, apoptosis, maintenance of stemness, and remodeling of the tumor microenvironment. Furthermore, members of the miR‑200 family have potential as diagnostic and prognostic biomarkers and are closely linked to chemotherapy resistance. The present review aims to provide novel insights and a theoretical foundation for the diagnosis, treatment, and deeper investigation of BC by comprehensively examining the functional mechanisms of the miR‑200.

Targeting glycolysis in prostate cancer: Molecular mechanisms and therapeutic advances.

Advances in pyrimidine-like heterocyclic scaffolds: Innovative synthetic method for malic enzyme inhibition in pancreatic ductal adenocarcinoma (PDAC) - A comprehensive review.

Aspirin is widely used as an antiplatelet therapy for preventing and managing thrombotic complications in individuals at high risk. Nevertheless, growing evidence indicates that some patients continue to face cardiovascular events, suggesting impaired drug responsiveness or reduced sensitivity to aspirin. This review primarily aims to elucidate a new emerging molecular mechanism underlying this clinical outcome. Recent studies propose that aspirin induces PPARα-dependent overexpression of the Multidrug Resistance Protein 4 (MRP4) transporter, leading to increased extrusion of aspirin and reduced drug efficacy. Several findings support this mechanism: i) MRP4 is associated with resistance to several drugs; ii) it is highly expressed in platelets, which are notably affected by aspirin; iii) it transports organic anions such as aspirin, which has been demonstrated to be a substrate; and iv) aspirin enhances PPARα activity, leading to higher MRP4 gene transcription. Consequently, inhibition of MRP4-mediated aspirin efflux may enhance pharmacological efficacy and prevent platelet aggregation. This review also highlights the potential role of lifelong monitoring in patients on aspirin therapy using platelet function tests to identify those with high residual platelet reactivity (RPR) despite treatment. Such monitoring helps detect inadequate antiplatelet response, guiding clinicians in selecting the most appropriate and personalised therapy, thereby optimising treatment efficacy and reducing the risk of recurrent thrombosis. In conclusion, combining an MRP4 inhibitor with aspirin may represent a promising therapeutic strategy to overcome resistance mechanisms and improve clinical outcomes in patients who exhibit RPR on aspirin and MRP4 overexpression.

From code to cancer: CircRNAs and lncRNAs regulate kinesin functions in tumorigenesis.

Cancer Stem Cells (CSCs) represent a heterogeneous group of tumor cells that possess the innate ability to self-renew and differentiate, which also contributes to their resistance to first-line therapies. What sets CSCs apart from others is their crucial role in the recurrence of cancer, metastasis, and varied clinical responses against anti-cancer drugs, which makes them challenging to target. In recent years, there has been growing evidence that therapies capable of eliminating CSC niches or specifically targeting their core survival mechanisms are a potential means of providing a sustainable, long-term response to therapy and increasing disease-free survival rates. Bioactive compounds from natural sources have gained immense interest for their bio-efficacy, low toxicity profiles, and wide therapeutic index (TI), especially with their broad-spectrum ability of targeting multiple pathways while having little or no systemic side effects. Bioactive compounds can target major signaling pathways (Wnt/β-catenin, Notch, Hippo-YAP/TAZ, Hedgehog, PI3K/Akt/mTOR, NF-κB) to induce apoptosis, inhibit epithelial-mesenchymal transition (EMT), disrupt cancer stem cell niches, and other effects that suggest they resensitize to chemotherapeutic agents. Plant-derived biologics may be used as unique strategies targeting CSCs or as adjuncts reconstituted with custom conventional treatment plans, to mitigate drug resistance with mechanisms that involve targeting CSC metabolism, blocking protective autophagy, and the epigenetic landscape. The use of nanotechnology for targeted delivery of bioactive compounds is anticipated to provide better stability, bioavailability, and tumor accumulation. In this review, we outline a range of approaches using bioactive compounds for the eradication of CSCs, focusing on the mechanisms by which they work, the preclinical and clinical evidence supporting them, and their role in combination therapy approaches. This review also gives a comprehensive understanding of various other strategies and latest advancements that do not directly target the CSCs, including differentiation therapy, metabolic targeting, and immunomodulation, which, when used in conjunction with bioactive compounds, may resensitize the drug-resistant CSC population. We also discuss the therapeutic and translational potential of bioactive compounds and the future possibilities of combination, multi-targeted, CSC-based treatment strategies to eliminate tumor recurrences and improve cancer outcomes for patients.

Multiple myeloma (MM) is an incurable hematologic malignancy characterized by the clonal expansion of plasma cells in the bone marrow. Despite advances in therapeutic agents, including proteasome inhibitors, immunomodulatory drugs and immunotherapies, relapse driven by treatment resistance remains a major clinical challenge. This underscores the critical need to elucidate additional molecular mechanisms that drive MM pathogenesis and therapeutic failure. The emerging field of epitranscriptomics, which studies post‑transcriptional RNA modifications, offers a promising perspective. Among these modifications, N6‑methyladenosine (m6A), the most abundant internal mRNA modification, has been implicated in regulating nearly every aspect of RNA metabolism. Growing evidence indicates that dysregulation of the m6A modification machinery plays a pivotal role in MM heterogeneity, disease progression and drug resistance. The present review synthesized current knowledge on how specific m6A regulators contribute to MM oncogenesis by modulating key signaling pathways, interactions with the bone marrow microenvironment and responses to therapy. It also discussed the potential of targeting m6A pathways as a therapeutic strategy to overcome treatment resistance and improve patient outcomes. By highlighting recent advances and future directions, the present review underscored m6A modification as an important frontier in the battle against MM.

Dendritic cells targeted CEA tumor antigen through DEC205 in combination with oncolytic reovirus stimulate strong immune response in colorectal cancer model.

M1C mediates LINE-1 transcription in PARP inhibitor-treated prostate cancer cells.

Spatial-single cell multiomics reveals TRIM44-driven Treg differentiation and drug resistance in AML: Therapeutic reversal by Sinomenine.

Fifty years of chicken-source Salmonella in China: Evolutionary shifts in epidemiology, antimicrobial resistance, and genomic lineages.