Due to the lesion's inoperable location and risk of vascular and biliary compression, targeted therapy with the MEK inhibitor selumetinib was indicated. The patient is currently awaiting provision of the medication. This case underscores the importance of careful monitoring and early initiation of targeted therapy in NF1 patients with extensive plexiform neurofibromas, particularly those caused by large NF1 gene deletions, which result in complete loss of neurofibromin and extensive infiltrative benign tumor growth.

Targeted therapy with trametinib achieved partial radiologic response before further progression. The patient remains clinically stable under ongoing therapy and multidisciplinary care. This case underscores the critical role of molecular diagnostics in risk stratification and treatment selection, particularly in infants with atypically aggressive PLGG.

P2, N=57, Active, not recruiting, University Health Network, Toronto | Trial completion date: Sep 2026 --> Sep 2027 | Trial primary completion date: May 2026 --> May 2027

Patients with specific chimeric RNAs, such as BRAF and JAK2, exhibited favorable responses to trametinib or ruxolitinib, and those with more neoantigens may benefit from immunotherapy. In subcutaneous xenograft models, tumors bearing Ctsc-Rab38 responded better to anti-PD1 therapy, highlighting its potential as a biomarker and therapeutic target. These findings indicate that chimeric RNAs can produce novel fusion proteins and neoantigens, disrupt the expression and function of partner genes, and guide clinical treatment stratification in ESCC.

P1, N=16, Active, not recruiting, Pfizer | Recruiting --> Active, not recruiting

P1, N=50, Recruiting, University of California, San Francisco | Suspended --> Recruiting

Drug sensitivity profiling revealed ST3GAL4 exhibited strong correlations with AZ628 (pan-RAF inhibitor) and RDEA119 (MEK inhibitor), which was further validated by molecular docking showing excellent binding affinities (binding energies: -8.7 and - 7.2 kcal/mol). This study provides structural evidence for targeted therapeutic strategies in ST3GAL4-overexpressing melanoma and establishes foundations for age-stratified immunotherapy.

Furthermore, we use the 3D NC spheroid models to discover drugs targeting MPNSTs through high-throughput screening of epigenetic compounds. Poly(ADP-ribose) polymerase inhibitors (PARPi) exhibit selective efficacy in PRC2-deficient NC spheroids and Olaparib-Selumetinib combination is well tolerated and significantly suppresses tumor growth in a human MPNST PDX mouse model.

P=N/A, N=82, Completed, Novartis Pharmaceuticals

P1, N=3, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Recruiting --> Active, not recruiting | N=23 --> 3

This regimen is highly clinically accessible and may serve as a second-line treatment option when KRAS G12C-specific inhibitors are unavailable. Its clinical value requires further validation through large-sample prospective studies.

As a result, we found that any possible 2-drug combination of venetoclax, ponatinib, and trametinib was highly synergistic in vitro. Regrettably, none of the synergistic 2-drug combinations appeared sufficiently effective in preventing leukemia outgrowth in our PDX models, which likely requires combinations of >2 drugs. Hence, our results illustrate/signify that straightforward high-throughput combinatorial drug screening in leukemia cell lines is a valid approach to identify synergistic drug combinations that are verifiable in vivo in PDX mouse models without requiring validation in primary patient cells in vitro.