HEY1 (Hes Related Family BHLH Transcription Factor With YRPW Motif 1)

This multicentre study confirms that anthracycline-based regimens show activity in MCS, with responses more in line with soft tissue sarcoma than Ewing sarcoma. Their benefit in localized disease remains uncertain, but (neo)adjuvant chemotherapy with Ewing-like regimens should be considered for patients eligible for surgery. In advanced disease, trabectedin may provide prolonged disease control after anthracyclines.

In xenograft models, TPP accelerated tumor growth. Collectively, these data position TPP as an environmental accelerator of ECM-mechanics-proliferation circuitry in GC and highlight druggable nodes of therapeutic and regulatory relevance.

The consistent alterations suggest the presence of a shared Notch-driven oncogenic signature in breast cancer, potentially driving cell proliferation, stemness, and resistance to therapy. These findings enhance our understanding of Notch signaling in breast cancer and propose novel miRNA-Notch interactions as candidate targets for therapeutic intervention.

The effect in Orai expression mediated by activation of Notch1 signaling pathway was mimicked by the expression of HEY1 or the non-phosphorylatable HEY1-S68A mutant; by contrast, expression of the phosphomimetic HEY1-S68D mutant was without effect on Orai expression. Understanding the Notch1-HEY1-Orai axis might provide insights into the development of subtype-specific therapeutic strategies targeting breast cancer.

Trabectedin demonstrates low disease control rate in translocation-related sarcomas, including few MCS cases. Anti-angiogenic tyrosine kinase inhibitors, such as apatinib and pazopanib, demonstrate activity in chondrosarcoma, but MCS-specific data are lacking. IDH1 inhibition benefits conventional subtypes rather than MCS. Early immunotherapy experience is limited, but pathway-directed strategies targeting BCL2 and PI3K-mTOR warrant evaluation.

P2, N=16, Recruiting, Italian Sarcoma Group | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Aug 2025 --> Dec 2025

Upregulated MGP promotes cancer cell adhesion to LN lymphatics. Thus, breast cancer cell metastasis to LNs remodels LEC subsets in human LNs and escalates MGP expression, potentially facilitating cancer cell dissemination through the lymphatic system.

The changes identified indicate a complex reprogramming of transcriptional activity affecting cell cycle processes, DNA repair, metabolism, and the epithelial-mesenchymal transition. The findings expand our understanding of the molecular mechanisms of trastuzumab resistance and open prospects for the development of novel therapeutic strategies to overcome drug resistance in HER2-positive breast cancer.

LIN28B activation via promoter hypomethylation defines a high-risk JMML subgroup with cell cycle. Methylation-based stratification predicts survival, positioning LIN28B as a therapeutic target.

Following the removal of dumbbell-shaped MCS, the dura mater may require repair. While histopathological evaluation remains the gold standard for confirming a diagnosis of MCS, the HEY1::NCOA2 fusion gene is a specific molecular marker for MCS, and the presence of this gene has become a powerful tool for diagnosis.

By targeting both intrinsic and extrinsic apoptotic pathways, Boldine effectively inhibits tumor growth. These results position Boldine as a promising candidate for developing anticancer therapies aimed at aggressive malignancies such as KB and HEp-2 cells.

The levels of P-gp, MRP-1, cleaved-CASP3, P53, HIF-1α, PI3K, p-AKT, and p-ERK1/2 decreased while the pro-CASP3 level was diminished in CVL + PTX-treated cells. Our findings suggest that CVL could be repurposed as a co-treatment candidate, capable of overcoming PTX resistance, inducing apoptosis, enhancing miR-34a expression, reducing the expression of efflux transporters, and inhibiting essential survival signaling pathways.