dactinomycin

Our work uncovers a previously unrecognized PRKN-METTL3-CLDN2 signaling network that orchestrates colorectal tumorigenesis, providing a compelling rationale for developing METTL3-targeted therapies against CRC.

Our findings establish the ALKBH5/IGF2BP1-TRIM37-RBMX signaling axis as a pivotal driver of PDAC progression, highlighting the intersection of m6A modification, ubiquitin signaling, and metabolic reprogramming. These findings may provide potential therapeutic avenues for this intractable malignancy.

We have established the circ-ZBTB38/RALGAPB axis as a novel regulatory circuit in melanoma. Circ-ZBTB38 mediates RALGAPB post-translational degradation to hyperactivate Ral signaling. This work uncovers a new mechanism of circRNA-mediated regulation of enzyme activity (RalGAPs) in signaling crosstalk and highlights circ-ZBTB38 as a prognostic biomarker and therapeutic target for melanoma.

Here, we demonstrate that expression of DYRK1B - but not its closely related paralog DYRK1A - is upregulated by cytostatic drugs (Actinomycin D, Doxorubicin) in multiple cancer cell lines. In conclusion, our study identifies DYRK1B as an indirect p53 target that suppresses p53-mediated activation of RFX7. These findings suggest that pharmacological inhibition of DYRK1B may represent a therapeutic strategy to enhance RFX7 tumor suppressor function.

The patient was treated with VAC chemotherapy (vincristine, actinomycin D, cyclophosphamide), local radiotherapy (60 Gy), cranial prophylactic radiotherapy (12 Gy), and subsequent debulking surgery. Multimodal treatment incorporating chemotherapy, radiotherapy, surgery, and targeted maintenance therapy can achieve meaningful disease control in aggressive craniofacial MCS. To our knowledge, this represents one of the very few reported pediatric cases of maxillary MCS with confirmed HEY1::NCOA2 fusion managed with sirolimus-based maintenance therapy.

We induce a patient-derived xenograft model (KT-47) to develop blastemal predominance after chemotherapy and to become resistant to vincristine, actinomycin-D, and doxorubicin (VAD). These findings are validated in additional Wilms tumor models. Overall, resistance is associated with de-differentiation to a stem-like state and is driven by ABCB1 upregulation, suggesting that therapeutic strategies targeting chromatin regulation and drug efflux may be relevant in therapy-resistant Wilms tumor.

P3, N=395, Active, not recruiting, Children's Oncology Group | Trial completion date: Mar 2026 --> Nov 2026

The interaction between SNRPA1 and METTL3 or IGF2BP2 was studied using RIP assay, dual-luciferase reporter assay, and actinomycin D assay, while the association of SNRPA1 with TWIST was determined through Co-IP assay and CHX assay...The METTL3/IGF2BP2-mediated m6A methylation modification of SNRPA1 binds to TWIST1 to promote NSCLC cell proliferation, migration, and invasion, ultimately leading to NSCLC progression. The online version contains supplementary material available at 10.1007/s10616-026-00924-w.

P3, N=342, Not yet recruiting, Children's Oncology Group

Two relapsed patients received salvage chemotherapy [vincristine-actinomycin D-cyclophosphamide (VAC) or ifosfamide-carboplatin-etoposide (ICE)], which showed limited efficacy. One relapsed patient with TPM3::NTRK1 received larotrectinib but died two months later; another with EGFR-KDD experienced disease stabilization after afatinib plus programmed cell death protein 1 (PD-1) blockade following progression on entrectinib and anlotinib...While most patients experienced favorable outcomes following surgery, relapsed cases highlight the challenges associated with molecularly atypical disease. These observations are descriptive in nature and underscore the need for larger collaborative studies to better define prognostic factors and optimal management strategies in CMN.

ARPC1B drives GC progression by stabilizing HK2 mRNA through IGF2BP3 binding, thereby potentiating glycolytic reprogramming to facilitate tumor growth and metastasis. Targeting the ARPC1B-IGF2BP3-HK2 axis may represent a novel therapeutic strategy for GC.

Ovarian cancer is highly lethal, largely due to the rapid development of paclitaxel resistance...RNA pull-down, RNA immunoprecipitation (RIP), and actinomycin D mRNA decay assays were conducted to elucidate the molecular interactions between lncRNA-PRLB, the RNA-binding protein fused in sarcoma (FUS), and glutathione peroxidase 4 (GPX4) mRNA...This study identifies lncRNA-PRLB as a critical upstream regulator of ferroptosis resistance and chemoresistance in ovarian cancer. By scaffolding FUS to stabilize GPX4 mRNA, lncRNA-PRLB maintains GPX4 expression and enables tumor cells to evade ferroptotic cell death.