P2, N=16, Active, not recruiting, Verastem, Inc. | Recruiting --> Active, not recruiting

P1, N=14, Active, not recruiting, Emory University | Trial completion date: Oct 2026 --> Dec 2027 | Trial primary completion date: Oct 2025 --> Dec 2026

Oral melanocytic neoplasms are rare and have distinct clinicopathological features. Despite this, a gap exists in molecular data regarding ODN and AMP. Conversely, OMN and OMM have distinct profiles; in particular, the latter may benefit modestly from tyrosine kinase inhibitor treatment, as KIT and BRAF mutations are sensitive to imatinib and vemurafenib, respectively.

Although vemurafenib showed efficacy in metastatic melanoma, off-label use resulted in limited benefit and increased adverse events. Unclear endpoints and underreported adverse events highlight the need for improved clinical trial design.

P1, N=15, Recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: May 2026 --> Jun 2027 | Trial primary completion date: Dec 2025 --> Jun 2026

P1, N=26, Active, not recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial completion date: Nov 2025 --> Nov 2026

Our findings reveal the role of the BMAL1-LHX8 axis in underlying AMF-mediated drug resistance in AM, and propose that the molecular clock modulation in tumor-stroma crosstalk represents a potential therapeutic avenue for ameloblastoma.

This PEITC effect could be demonstrated in two further dabrafenib-resistant cell lines, WM164D and 451LuP. These results suggest that the altered redox status is linked to compromised mitochondria and is associated with the development of BRAFi resistance, rendering cells exquisitely sensitive to the actions of selective ROS-inducing therapeutics.

Cutaneous melanoma cell lines (A375 and SK-MEL-28) were transfected by CENPM siRNA (si-CENPM), followed by detections and treatment of various concentrations of dabrafenib and vemurafenib. Clinically, GEPIA database revealed that CENPM was upregulated and correlated with worse overall survival in cutaneous melanoma patients. Targeting CENPM suppresses cutaneous melanoma growth and mobility by inactivating AKT pathway, indicating its potential as a treatment target.

Critically, the 3D microenvironment induced a more aggressive phenotype, characterized by upregulated expression of the BRAF V600E oncogene and the induction of epithelial-mesenchymal transition (EMT), and conferred significantly increased resistance to both cisplatin and vemurafenib. These findings indicate that our tissue-specific, TAS-based 3D model successfully recapitulates key pathophysiological hallmarks of thyroid cancer, representing a more clinically relevant and predictive platform for investigating tumor mechanisms and for the preclinical evaluation of novel therapeutic agents.

Preclinical studies show that pharmacological inducers, including vitamin C, tenacissoside H, neferine, curcumin, and shikonin, as well as targeted agents such as dabrafenib and anlotinib, can trigger or synergize with ferroptosis. Although systemic toxicity and resistance remain obstacles, biomarker-driven selection and drug repurposing offer promise. Ferroptosis represents a mechanistically distinct and clinically exploitable pathway for ATC.