Mekinist (trametinib)

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.

We established a PDX model of MLA to facilitate personalized treatment for rare tumors.

Despite substantial advances, secondary mutations and reactivation of oncogenic signaling remain major challenges. This narrative review integrates data from clinical, preclinical, and real-world studies to update the current understanding of targeted therapies in cutaneous melanoma and highlight ongoing research aimed at overcoming resistance and optimizing personalized treatment strategies.

Molecular events included the emergence of a BRAF V600E mutation responsive to dabrafenib plus trametinib and the acquisition of an EGFR exon 19 deletion responsive to Osimertinib. EVA/PCD identified activity for targeted agents and revealed synergy for vinorelbine plus Osimertinib not predicted by genomic profiling, which provided additional response. This case highlights clonal evolution in NSCLC and illustrates how serial tissue analyses correlating phenotypic and genomic events can offer therapeutic interventions to provide long-term survival. The integration of functional and genomic profiling may improve personalized treatment in NSCLC by interrogating tumor heterogeneity and clonal evolution to inform rational therapeutic selection.

In this single-center retrospective cohort, neoadjuvant-plus-adjuvant dabrafenib and trametinib was feasible, enabling timely surgery with manageable toxicities. Survival outcomes were comparable to adjuvant-only therapy, and pathological responses in the neoadjuvant cohort provide exploratory prognostic information.

This study establishes a PANoptosis-derived prognostic model with moderate but consistent prognostic utility across platforms, underscoring its potential research value. By linking PRGs to risk stratification and immune heterogeneity, the model provides insights into PANoptosis biology and supports future exploration of personalized immunotherapy in cervical cancer.

mTOR and PI3Kα inhibitors such as sirolimus and alpelisib have shown promising efficacy in slow-flow VMs, while reports have suggested that MAPK inhibitors such as trametinib may improve arteriovenous malformations. Emerging approaches such as mutant-selective inhibitors, proteolysis-targeting chimeras, and gene therapy hold promises for improving treatment specificity and minimizing adverse effects. This review provides an overview of the genetic bases of VMs, recent advances in targeted therapies, and future directions in the field, highlighting the ongoing evolution of precision medicine for VMs.

P1, N=89, Completed, C4 Therapeutics, Inc. | Active, not recruiting --> Completed | Trial completion date: Apr 2027 --> Nov 2025 | Trial primary completion date: Mar 2027 --> Nov 2025