FAM83A promotes MASH pathogenesis by interacting with RAF1 to activate ERK signaling, thereby stimulating fatty acid and cholesterol biosynthesis. Targeting this axis may offer therapeutic potential for MASH and metabolic dyslipidemia.

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.

This study highlights the clinical and healthcare challenges of NF1 and PN in Saudi Arabia, emphasizing the need for a multidisciplinary approach that combines medical, psychological, and financial support. The limited access to Selumetinib represents a gap. Increasing treatment accessibility and financial support are key to improving the outcomes and QoL.

Here we show that the BET inhibitor PLX51107 potently suppresses the growth of NRAS -mutant AML cell lines, and that these activities are enhanced by co-treatment with the MEK inhibitor PD0325901. AMLs that relapsed after frontline chemotherapy showed similar transcriptional remodeling. These studies demonstrate transcriptional plasticity in primary AMLs that relapse following in vivo treatment with either targeted agents or chemotherapy, and support evaluating BET inhibition in leukemias with monocytic differentiation and RAS mutations.

The exarafenib plus binimetinib combination demonstrated superior efficacy in diverse preclinical models. This study establishes ARAF-KSR1 complex formation as a novel resistance mechanism to pan-RAF inhibition and provides mechanistic rationale for combination strategies with potential to address the unmet clinical need for BRAF Class II and III-mutated NSCLC.

Drug sensitivity analysis revealed enhanced efficacy of agents like selumetinib in high-APOA1 tumors. This integrated, cross-layer evidence positions APOA1 as a tumor suppressor and actionable biomarker in LUAD, with implications for early detection, therapeutic stratification, and immunomodulatory strategies.

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.

P2, N=1000, Active, not recruiting, Melanoma Institute Australia | Recruiting --> Active, not recruiting | Trial primary completion date: Jul 2027 --> Nov 2025

P2, N=24, Active, not recruiting, Providence Health & Services | Trial completion date: Oct 2027 --> Jan 2027 | Trial primary completion date: Oct 2025 --> Jan 2026