Koselugo (selumetinib)

P2, N=57, Active, not recruiting, University Health Network, Toronto | Trial completion date: Dec 2025 --> Sep 2026 | Trial primary completion date: Dec 2024 --> May 2026

P2, N=41, Not yet recruiting, University of Alabama at Birmingham | Trial completion date: Dec 2031 --> May 2032 | Trial primary completion date: Dec 2030 --> May 2031

Selective BRAF and MEK inhibitors-including vemurafenib, dabrafenib, and selumetinib-have demonstrated efficacy in advanced thyroid cancers. The combination of dabrafenib and trametinib is FDA-approved for BRAF V600E-mutant anaplastic thyroid carcinoma (ATC) based on its significant survival benefits...Additionally, redifferentiation strategies using MAPK inhibitors to restore RAI avidity have shown promise, particularly in selected patients. These advances highlight the need to contextualize BRAF mutation status within a broader molecular and clinical framework to guide personalized, effective treatment strategies.

Dabrafenib plus trametinib has shown superiority over chemotherapy in pediatric low-grade gliomas and activity against high-grade diseases. Larotrectinib and entrectinib provide tumor-agnostic options for NTRK-fusion-positive tumors with central nervous system penetration. Selumetinib offers clinical benefits in NF1-associated plexiform neurofibromas and shows promise for treating NF1-related low-grade gliomas. Tovorafenib, a type II RAF inhibitor active in BRAF-altered tumors (including BRAFKIAA1549 fusion), achieved robust responses, thereby leading to FDA approval. ONC201 (dordaviprone) has received accelerated approval for the treatment of H3 K27M-mutant diffuse midline gliomas, with Japanese trials and patient-initiated programs expanding access. Abemaciclib, a CDK4/6 inhibitor, is under phase II evaluation for pediatric high-grade glioma and diffuse midline glioma, including sites in Japan. Neurosurgeons play a pivotal role in securing high-quality biopsies, thus enabling comprehensive molecular diagnostics and facilitating enrollment in international trials. This review summarizes current targeted therapies and ongoing studies and outlines practical considerations for integrating precision oncology into pediatric neuro-oncology in Japan.

Selumetinib, entinostat, and erlotinib were identified as candidate drugs for cluster 2, whereas tozasertib, alpelisib, and cediranib showed higher suitability for cluster 1. Ten potential biomarkers, 13 transcription factors, and 2 miRNAs were characterized. This study elucidates the role of UPS in ESCC progression and provides a framework for personalized treatment strategies.

This pan-cancer study elucidates the pivotal role of ENTPD6 in tumor progression and establishes its potential as a therapeutic target for immunotherapeutic approaches in specific malignancies.

This study highlights the clinical and healthcare challenges of NF1 and PN in Saudi Arabia, emphasizing the need for a multidisciplinary approach that combines medical, psychological, and financial support. The limited access to Selumetinib represents a gap. Increasing treatment accessibility and financial support are key to improving the outcomes and QoL.

Drug sensitivity analysis revealed enhanced efficacy of agents like selumetinib in high-APOA1 tumors. This integrated, cross-layer evidence positions APOA1 as a tumor suppressor and actionable biomarker in LUAD, with implications for early detection, therapeutic stratification, and immunomodulatory strategies.

Selumetinib alters gene expression of hiPSC-derived RPE, with significant changes in genes involved in transport of ions and small molecules regulating cell volume and lysosomal acidification. Selumetinib may lead to subretinal fluid accumulation by both increasing secretions into this space and decreasing outflow.

P1/2, N=40, Completed, M.D. Anderson Cancer Center | Active, not recruiting --> Completed

In this study, we established chemoresistant uveal melanoma cell lines by exposing parental cells to dacarbazine, cisplatin, or gemcitabine and performed high-throughput drug screening incorporating normal human epidermal melanocytes (NHEMs) as a normal control to assess both efficacy and selectivity. Our screening identified temsirolimus and selumetinib as top candidates, with temsirolimus exhibiting strong tumor-selective cytotoxicity...Mechanistically, temsirolimus downregulated mammalian target of rapamycin (mTOR) signaling, as indicated by reduced p-mTOR, p-S6, and p-4EBP1 expression in tumor tissues. These findings demonstrate that temsirolimus selectively targets chemoresistant uveal melanoma cells, enhances chemotherapy efficacy, and suppresses tumor growth via mTOR inhibition, supporting its potential clinical application as a novel therapeutic strategy for chemoresistant uveal melanoma.

However, the disease recurred 6 months later, prompting the initiation of carboplatin therapy. Primary treatment with MAPK kinase inhibitors can lead to tumor regression in brainstem glioma in an adult patient with NF1. We recommend that patients with brainstem glioma undergo biopsy and mutation testing, especially those with an unusually aggressive clinical course.