Redifferentiation approaches using MAPK pathway inhibitors such as selumetinib and dabrafenib can restore iodine uptake in selected patients, although the overall clinical applicability of these strategies remains under evaluation. A better understanding of these mechanisms may support improved biologic stratification and more selective therapeutic decision-making in radioiodine-refractory DTC.

P2, N=25, Completed, Stanford University | Recruiting --> Completed | Trial completion date: Dec 2024 --> Feb 2026 | Trial primary completion date: Dec 2024 --> Feb 2026

P2, N=45, Active, not recruiting, Children's Hospital of Philadelphia

P1/2, N=229, Completed, Centre Leon Berard | Active, not recruiting --> Completed

Moxibustion can enhance the anti-tumor effect of Trametinib by inhibiting the phosphorylation of MEK/ERK pathway and the downstream c-Myc/PD-L1 axis in mice with breast cancer, which provides an experimental basis for the adjuvant targeting therapy of breast cancer with moxibustion.

P4, N=0, Withdrawn, SRH Wald-Klinikum Gera GmbH | N=101 --> 0 | Not yet recruiting --> Withdrawn

Higher selumetinib exposure appears to be associated with treatment-related adverse effects in pediatric NF1 patients. These findings support the potential role of TDM in optimizing selumetinib dosing and provide a preliminary therapeutic AUC range for individualized treatment strategies. Larger multicenter studies are needed to validate these results and refine exposure-guided dosing approaches.

P1/2, N=26, Recruiting, Memorial Sloan Kettering Cancer Center

The authors discuss adverse event management and the implications for integration into routine clinical practice. Clinicians caring for patients with low-grade serous ovarian carcinoma can use the drug knowledge and evidence outlined in this review to assist with implementing avutometinib and defactinib therapy.

Selumetinib treatment was associated with a significant, consistent, and durable decline in prescription pain medication utilization over 3 years. Patients who continued taking pain medications experienced nominal dose reductions, and patients who received selumetinib continuously experienced a decrease in prescription pain medication utilization.

P2, N=145, Active, not recruiting, Laura Huppert, MD, BA | Recruiting --> Active, not recruiting | Trial completion date: Jun 2026 --> Jan 2027 | Trial primary completion date: Jun 2026 --> Jan 2027

Map2k4 mutant cells were particularly sensitive to paclitaxel, and Rho kinase inhibitor (ROCKi) increased trametinib sensitivity in both Map2k4- and Nf1-mutant organoids. This organoid mutagenesis strategy is powerful for unraveling the genetic and phenotypic complexity of HGSC, and identified Map2k4 as a potential therapeutic target in select HGSC cases.