Cutaneous Melanoma

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.

P2, N=150, Active, not recruiting, ECOG-ACRIN Cancer Research Group | Recruiting --> Active, not recruiting

Both imiquimod and gardiquimod treatment inhibited tumor growth, with gardiquimod showing an increased potency compared to imiquimod. This implies that TLR agonists like imiquimod and gardiquimod could serve as neoadjuvant, adjuvant, or complementary immunotherapeutic agents in melanoma therapy.

Profiling inflammatory mediators revealed significant modulation upon treatment with SMO inhibitors, possibly affecting chemotactic and immune functions. Collectively, these findings provide deeper insight into the role of the Hh pathway in melanoma and support the potential repurposing of Hh inhibitors as therapeutic agents for melanoma.

TM promotes melanoma cell plasticity and VM through FAK- and ezrin-dependent pathways. These findings position TM as a key regulator of tumor progression and suggest that targeting TM may offer a novel therapeutic strategy to disrupt cancer cell plasticity and suppress melanoma growth.

By conducting transcriptomic identity, lineage-traced ontogeny, surface marker expression and functional studies, we identified and characterized this DC population. Our data demonstrated that TSLP acts on transitional dendritic cell-derived DC2 to promote GATA3+ eTreg cells, thus uncovering a previously unrecognized tolerogenic axis in promoting immunosuppression, which is likely conserved in humans, across contexts of inflammation and cancer.

P1/2, N=16, Active, not recruiting, National Cancer Institute (NCI) | N=58 --> 16 | Trial completion date: Nov 2025 --> Jan 2027

P1, N=800, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Oct 2025 --> Oct 2026 | Trial primary completion date: Oct 2025 --> Oct 2026