Cutaneous Melanoma

P2, N=267, Active, not recruiting, ModernaTX, Inc. | Recruiting --> Active, not recruiting | Trial completion date: Sep 2029 --> Nov 2032 | Trial primary completion date: Sep 2029 --> Nov 2032

In summary, the dacarbazine-2-AEH2P combination exhibits synergistic pharmacodynamic activity that enhances cytotoxicity through coordinated modulation of proliferative and apoptotic pathways. These findings highlight its potential as a promising strategy to improve chemotherapeutic efficacy and overcome resistance in melanoma treatment.

P1, N=3, Terminated, Mayo Clinic | Trial completion date: Jan 2026 --> Feb 2025 | Active, not recruiting --> Terminated | Trial primary completion date: Jan 2026 --> Feb 2025; low/slow accrual

P=N/A, N=73, Completed, Memorial Sloan Kettering Cancer Center | Active, not recruiting --> Completed | Trial completion date: Mar 2026 --> Nov 2025 | Trial primary completion date: Mar 2026 --> Nov 2025

The study also identified six key genes, among which both the silencing and overexpression of GALNT2 significantly affect the proliferation and migration of melanoma cells. This study highlights the significance of MRGs in predicting patient survival and immunotherapy outcomes, providing insights for potential future targeted therapies.

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.

About 40% of cutaneous melanomas carry BRAF mutations-more common in younger patients-and these are linked to more aggressive behaviour and a higher risk of brain metastasis. Over the past decade, targeted therapies (TT) using BRAF and MEK inhibitors (BRAFi, MEKi), along with immune checkpoint inhibitors (ICI), have significantly improved response rates and survival in metastatic melanoma.

These findings establish for the first time that SEMA5A is a novel player of melanoma aggressiveness and progression, modulating cancer cell viability and migration, focal adhesion signaling and lamellipodia formation in vitro and tumor growth in vivo.

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.

Our findings reveal a novel WTAP-KLF9 axis that mediates melanoma suppression through m6A-dependent regulation. This study provides new insight into the context-specific role of WTAP in melanoma and suggests it may serve as a potential biomarker or therapeutic target.

Yet, clinical integration requires multicentric validation, standardized protocols, and attention to workflow, ethical, and medico-legal challenges. Future developments, including multimodal AI and integration into molecular tumor boards, may redefine diagnostic precision in melanoma.

P=N/A, N=300, Recruiting, University of Modena and Reggio Emilia