PTEN (Phosphatase and tensin homolog)

Nanopore sequencing enables rapid, accurate, multidimensional molecular classification of diagnostically intractable CNS tumors using routine FFPE and frozen tissue, achieving high diagnostic resolution in comparison with reference methods while drastically reducing turnaround time and cost, making precision neuropathology feasible beyond quaternary centers.

Furthermore, we propose translational strategies for precision application: LKB1/PTEN status-based patient stratification, innovative combinations with CDK4/6 inhibitors, mTOR inhibitors, and immune checkpoint inhibitors, and clinical pathway optimization. By bridging metabolic endocrinology and gynecologic oncology, the available data provide preliminary theoretical basis to explore future shift of metformin from empirical off-label reuse toward biomarker-guided individualized medication, which still needs large-scale prospective validation.

CNOT9-deficient tumors exhibited reduced growth in mice, supporting its pro-oncogenic role. This study first elucidates the molecular mechanism by which CNOT9 drives HCC progression through post-transcriptional regulation of the PTEN/AKT/p53 axis, providing a theoretical basis for precision treatment strategies targeting CNOT9 or the PTEN/AKT/p53 pathway.

These coordinated pathways drive an "angiogenic switch," facilitate "metabolic migration," and induce significant resistance to chemotherapies, including gemcitabine and temozolomide. The hypoxamir-TAM axis is a fundamental driver of immune evasion and therapeutic failure. Targeting this dual-axis framework offers a viable strategy for restoring anti-tumor immunity, while circulating hypoxamirs represent high-value liquid biopsy biomarkers for real-time TME monitoring.

Collectively, the data support a shift from single-analyte biomarkers toward integrative, dynamic, systems-level models for patient selection, heralding a new era of precision immune-oncology in GC. However, most emerging biomarkers remain investigational and require prospective validation.

By seamlessly bridging real-world pharmacovigilance with advanced structural biology and single-cell transcriptomics, this study delineates the comprehensive safety landscape of capivasertib. Our findings provide crucial clinical alerts for AE monitoring and offer deep mechanistic insights to optimize personalized therapeutic management in breast cancer.

These findings highlight recurrent alterations in TP53, RB1, and ATRX and suggest potential roles for IGF2 and AXIN1 in leiomyosrcoma metastatic disease that warrant further investigation.

Importantly, therapeutic strategies aimed at interrupting viral miRNA function, restoring host tumor-suppressor pathways, and re-sensitizing tumor cells to immune surveillance hold promise. This review synthesizes current mechanistic insights into EBV-encoded miRNAs in oncogenesis, elaborates on their roles in lymphoma pathogenesis, and evaluates the translational potential of miRNA-targeted therapies in EBV-associated malignancies.

The findings underscore the limitations of tumor-only sequencing and current variant interpretation frameworks in admixed populations. Larger studies integrating matched normal DNA, ancestry-informed analyses, functional validation, and broader sequencing strategies could help improve variant interpretation in Latin American populations.

Notably, PRMT5 inhibitors demonstrate synergistic anticancer activity when combined with inhibitors of key oncogenic signaling pathways, including EGFR, PARP, and AKT. While several PRMT5 inhibitors are currently being evaluated in clinical trials for other malignancies, no clinical trials have yet been initiated specifically for TNBC.

scRNA-seq analysis suggests roles of epithelial-mesenchymal transition in the progression from carcinoma cells to sarcomatoid cells and in immunotherapy resistance in PSC. Altogether, this multi-omics characterization of PSC serves as a rich resource for investigating mechanistic insights and identifying potential therapeutic targets.

We highlight the recent results from the Phase III CAPItello-281 trial (NCT04493853) demonstrating that the addition of capivasertib to abiraterone acetate and androgen deprivation therapy (ADT) significantly improved radiographic progression-free survival in patients with PTEN-deficient mCSPC, leading to the FDA-approval of this regimen. Notable adverse events in the cabavisertib arm included hyperglycemia, diarrhea, and rash. CAPItello-281 addresses a significant unmet need for PTEN-deficient mCSPC, suggesting AKT inhibition as a potential new targeted treatment strategy for a sub-population with poor prognosis.