Cutaneous Melanoma

P2, N=20, Active, not recruiting, Melanoma Institute Australia | Trial completion date: Jan 2036 --> Oct 2035

P2, N=40, Withdrawn, Sydney Local Health District | Not yet recruiting --> Withdrawn

This study establishes a pan-skin cancer immune remodelling framework, providing a foundation for biomarker discovery and the development of new immunotherapy strategies.

Genetic testing identified a BRAF mutation, which led to the initiation of targeted therapy using dabrafenib in combination with trametinib. Therefore, implementing rigorous postoperative patient education and follow-up protocols is key to the early detection of recurrence and timely intervention. Simultaneously, the present case illustrates the challenge of acquired resistance to targeted therapy, underscoring the importance of developing strategies to overcome such resistance to potentially improve patient survival in the future.

P1, N=12, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting | N=38 --> 12

P1, N=65, Active, not recruiting, Genentech, Inc. | Trial completion date: Dec 2025 --> Jun 2027 | Trial primary completion date: Dec 2025 --> Jun 2027

HOXD13 orchestrates 3D enhancer-promoter contacts activating VEGFA, SEMA3A, and CD73, which remodel vasculature and elevate immunosuppressive adenosine. Consistently, HOXD13-induced tumor growth is reversed by combined VEGFR and adenosine receptor (AdR) inhibition, revealing a dual pro-angiogenic and immunosuppressive HOXD13 axis with therapeutic relevance.

Histopathologic evaluation revealed characteristic features of invasive melanoma, including atypical melanocytic nests, pagetoid spread, cytologic atypia, and architectural disorder. Overall, ACSL4 expression was significantly upregulated in primary cutaneous melanoma compared with normal skin, particularly within dermal atypical melanocytic tumor cells, suggesting that ACSL4 may contribute to melanoma biology through lipid metabolic pathways and may represent a potential biomarker of tumor aggressiveness, warranting further investigation into its diagnostic and prognostic relevance.

Therapies targeting specific genetic alterations and immunotherapy agents have been recently developed and introduced in clinical practice for the management of advanced-stage UMs. This review aims to present the latest advances in the clinical molecular pathology of UM, along with the resulting targeted, immunological, and other therapies that have been introduced or are currently under investigation.

IFNG, PTPN6, SLC38A1, and SOCS1 may serve as potential biomarkers of poor prognosis in SKCM patients. These genes demonstrate predictive value for immunotherapy response and drug sensitivity, particularly indicating susceptibility to selumetinib treatment, and therefore show substantial potential for clinical translation.

NRAS-mutant melanomas harbor a coordinated transcriptional program within 1p13.2, driven by CNV gains. This locus contains genes with potential druggability, offering new avenues for combinatorial targeting alongside mitogen-activated protein kinase pathway inhibition.