Mekinist (trametinib)

This exploratory analysis suggests pERK expression and mutation of KRAS/BRAF/NRAS are candidate biomarkers of improved PFS and response to trametinib, respectively.

The cooperative GOG 281/LOGS trial showed that trametinib, an MEK inhibitor (MEKi), was significantly more effective than standard-of-care options (including chemotherapy or hormonal therapy) in increasing progression-free survival (median PFS 13.0 months vs. 7.2 months; hazard ratio 0.48, p < 0.001)...Genomic and multi-omic profiling have revealed actionable vulnerabilities and precision oncology approaches. The advent of biomarker-directed trials, molecular subtyping incorporation, and innovative computational strategies is likely to gradually ameliorate therapy selection and, thereby, finally improve long-term outcomes for patients with this complex disease.

MEK inhibition with trametinib resulted in similar, yet more pronounced effects. Thus, our findings provide novel insights into NRAS-mediated signaling through nanoscale clusters and underscore their potential as therapeutic targets.

P2, N=200, Completed, Melanoma Institute Australia | Active, not recruiting --> Completed | N=1000 --> 200 | Trial completion date: Dec 2028 --> Dec 2025

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.

At the time of drafting this report, the patient had achieved 8 months of PFS. This case suggests that dose-adjusted dabrafenib combined with trametinib might be a potentially effective treatment strategy for elderly patients with advanced pancreatic adenocarcinoma harboring BRAF V600E mutations.

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.

The patient received combined dabrafenib, trametinib, and pembrolizumab with close safety monitoring, achieving rapid tumor control and complete remission by six months with manageable toxicity. This case suggests that early integration of PD-1 blockade with BRAF/MEK inhibition treatment may benefit selected patients and underscores the value of comprehensive molecular and immunohistochemical assessment to guide individualized therapy.

Importantly, this resistance mechanism is conserved in human melanoma: combined MEK and Gαq-PLCβ-PKC inhibition markedly enhances trametinib efficacy in BRAF V600E melanoma cells and xenografts, and reverses acquired resistance in trametinib-resistant melanoma sublines. Together, our results identify a conserved Gαq-PLCβ-PKC pathway as a driver of trametinib resistance and provide preclinical evidence for its co-targeting with MEK inhibition as a therapeutic strategy in BRAF V600E melanoma.

The ferroptosis inducer erastin also inhibits melanoma growth. Combining the ATAD2 inhibitor BAY-850 with the MEK inhibitor trametinib potently suppresses melanoma growth. Our study identifies ATAD2 as a key driver of melanoma and provides a rationale for targeting ATAD2 in conjunction with the MAPK pathway to treat melanoma.

This is the first report of trametinib-nintedanib for a 57-year-old KRAS G12D-mutated recurrent pancreatic ductal adenocarcinoma. He had transient remission (lower CA19-9, stable lesions) but died of gastrointestinal bleeding, showing efficacy and bleeding risk.

Furthermore, drug sensitivity predictions and validations suggest that SCD1 enhances the sensitivity of BCa cells to trametinib. Therefore, SCD1 offers a promising new avenue for the early diagnosis, prognostic assessment, and optimization of personalized treatment strategies for BCa.