Skin Cancer

P=N/A, N=60, Not yet recruiting, Jonsson Comprehensive Cancer Center | Trial primary completion date: Jun 2030 --> Dec 2030

Histological analysis revealed milder dysplasia in the cocoa-treated group compared to controls (p=0.002). Cocoa extract demonstrates potential as a natural chemopreventive agent against skin cancer through antioxidant activity, anti-angiogenesis, and apoptosis modulation pathways.

We demonstrate that MDM2 degraders KTX-049 and KT-253 overcome this limitation by collapsing the p53/MDM2 negative feedback loop. KTX-049 was >100-fold more potent than the MDM2 inhibitor DS-3032 across WT p53 MCC cell lines, and this superior potency was quantitatively supported by mechanistic mathematical modeling...Acquired resistance was strongly associated with acquisition of TP53 mutations, confirming on-target pathway pressure. These findings establish feedback architecture as a critical determinant of therapeutic response and position MDM2 degradation as a qualitatively distinct strategy that produces more durable pathway engagement than MDM2 inhibition, providing a preclinical rationale for prioritizing MDM2 degraders in WT TP53 MCC.

Despite histologic similarity, anogenital BCC demonstrates a distinct molecular profile, suggesting an alternative pathogenesis. Further genomic studies are warranted.

The e-DAM study demonstrates expert consensus that AMBLor™ could augment clinical decision making at key junctures in the cMM care pathway by refining SLNB selection, rationalising adjuvant therapy and imaging, and reducing follow-up burdens - enhancing personalised care, whilst alleviating service pressures.

FOXO3-mediated upregulation of HMOX1 promotes melanoma cell proliferation, invasion, immune escape, and ferroptosis resistance. The FOXO3/HMOX1 axis represents a potential therapeutic target for melanoma treatment.

P=N/A, N=280, Recruiting, National University Hospital, Singapore | Not yet recruiting --> Recruiting | Initiation date: Feb 2026 --> Jun 2026 | Trial primary completion date: Dec 2026 --> Jun 2027

However, in patients with BRAF-mutated melanomas, those who received BRAF inhibitors exhibited improved survival outcomes in advanced disease stages (p = 0.0025). Our study indicates that BRAF-mutated melanoma patients with distant metastases receiving BRAF inhibitors have significantly improved survival compared to those not receiving targeted therapy, supporting the clinical benefit of BRAF inhibitor use in appropriately selected patients.

Antibody depletion revealed that CIITA- and empty-transduced YUMMER.G tumors were constrained by CD4+ and CD8+ T cells, but only tumor growth of CIITA-transduced cells was decreased by CD25 blockade, which primarily blocks T regulatory cell function. Overall, this work reveals a potential pro-tumorigenic role of melanoma cell-specific overexpression of MHC class II.

Understanding the interplay between viral status, genomic burden, and the immune landscape is essential for overcoming ICI resistance. Rational combination strategies, particularly ICI plus radiation or epigenetic modulators to restore MHC-I expression, offer pathways to improve outcomes in resistant disease.

In vivo, WDR12 targeting sensitizes tumors to PD-1 blockade, and combined SU14813 and anti-PD-1 therapy produces superior antitumor efficacy. These results define a WDR12-CCT7-CD276 axis that sustains immune resistance in melanoma and nominate WDR12 inhibition with PD-1 blockade as a promising therapeutic strategy.

In IMvigor210, immunoproteasome-high patients achieved a 3.2-fold higher response rate to atezolizumab (19.8% vs 6.2%; p=0.010). Single-cell analysis confirmed that tumor-intrinsic immunoproteasome expression correlated with increased CD8+ T cell infiltration (p=0.0014) and total immune fraction (p=0.0002). The 4-gene immunoproteasome signature demonstrates robust prognostic and predictive value across bulk sequencing, clinical trial, and single-cell platforms, warranting prospective validation as an immunotherapy biomarker.