Mekinist (trametinib)

Genetic testing identified a BRAF mutation, which led to the initiation of targeted therapy using dabrafenib in combination with trametinib. Therefore, implementing rigorous postoperative patient education and follow-up protocols is key to the early detection of recurrence and timely intervention. Simultaneously, the present case illustrates the challenge of acquired resistance to targeted therapy, underscoring the importance of developing strategies to overcome such resistance to potentially improve patient survival in the future.

P1/2, N=57, Active, not recruiting, Pediatric Brain Tumor Consortium | Trial completion date: Jun 2030 --> Mar 2026 | Trial primary completion date: Mar 2027 --> Mar 2026

Treatment with the MEK inhibitor trametinib was initiated, but the patient died within three months. This case underscores the diagnostic challenges of EHE due to its rarity and variable clinical presentation, which often delays diagnosis until advanced stages. The report highlights the aggressive nature of pleural EHE and lack of standardised treatments, emphasising the need for early recognition.

Cells were treated with VEN, the MCL-1 inhibitor S63845 and the mitogen-activated protein kinase (MEK) inhibitor trametinib (TRA), alone or in combination. The presented results highlight the role of MAPK-driven MCL-1 and BCL(x)L expression, which mediates VEN resistance. While dual inhibition of B-cell lymphoma 2 and MCL-1 is already effective, additional MEK inhibition may further improve outcomes in PTPN11-mutated AML.

Tislelizumab can induce fulminant type 1 diabetes via immune-mediated mechanisms. Proactive monitoring of fasting glucose, HbA1c, and islet function is essential for patients with cancer receiving tislelizumab therapy.

The pharmacological inhibition of AKT (ipatasertib), MEK (trametinib), and RSK (BI-D1870) resulted in the reversal of ROS-induced effects, with the strongest effects observed upon the inhibition of YB-1 phosphorylation by BI-D1870. The results suggest that ROS exposure has a strong impact on cell migration and immune evasion not only in PM cells but also in mesothelial cells, from which PM arises. Interfering with ROS-responsive kinase pathways, particularly YB-1 phosphorylation, could counteract pro-migratory and immune-evasive effects in PM.

The individualized regimen comprised trametinib and everolimus for dual pathway inhibition, the tissue-agnostic agent dordaviprone (ONC201), metabolic modulation with 2-deoxy-D-glucose, and electric field-based therapy. The systematic integration of comprehensive molecular profiling with mechanistically rational treatment selection may contribute to meaningful radiological and clinical benefit in this otherwise uniformly fatal disease. These observations support further investigation of individualized, pathway-targeted approaches in prospective studies and N-of-1 trial frameworks.

P1/2, N=16, Active, not recruiting, National Cancer Institute (NCI) | N=58 --> 16 | Trial completion date: Nov 2025 --> Jan 2027

P4, N=165, Active, not recruiting, Novartis Pharmaceuticals | Recruiting --> Active, not recruiting

Ongoing combination strategies include MEK inhibition with type II RAF inhibitors (naporafenib plus trametinib in phase III trial), ERK1/2 or ERK5 inhibitors, PI3K/mTOR pathway blockade, or CDK4/6 inhibition. Additional investigational approaches include mutation-specific RAS inhibitors (G12C inhibitors already approved for other cancers), NRAS-specific or pan-RAS inhibitors (daraxonrasib in phase III trial for other cancers), targeted protein degradation, RAS-directed peptide and mRNA vaccines (mRNA-4157). NRAS Q61K-derived neoepitopes bound to HLA-A*01:01 have been recognized as immunogenic, suggesting that mutation-specific immunotherapies could represent a promising future strategy. In conclusion, the advent of promising and emerging therapies is set to transform the management of RAS-driven melanoma, making a personalized, biomarker-informed treatment strategy essential for optimizing patient outcomes.

Cassia-derived flavonoids represent promising multi-target candidates for lung cancer therapy, particularly through modulation of PTGS2, KIT, and XDH. Their favorable interaction profiles and safety predictions warrant further experimental and in vivo validation.

In pre-clinical PC, TIMP-1/CISS proves targetable through combined inhibition of upstream kinases with clinically approved drugs trametinib and nintedanib. Collectively, CISS represents a ubiquitous signature of pro-tumor immunoinstruction with actionable diagnostic and therapeutic potential across human cancers.