Merkel Cell Carcinoma

P2, N=27, Not yet recruiting, Mayo Clinic

Among skin carcinomas, RB1 inactivation is the hallmark of primary cutaneous neuroendocrine carcinoma commonly known as Merkel cell carcinoma (MCC), but it has also been described in other tumours including a subset of squamous cell carcinomas, sebaceous carcinomas and the recently described Wnt/beta-catenin-activated non-pilomatrical carcinomas. In this context, we provide a brief overview of the contribution of RB1 inactivation to oncogenesis and tumour cell phenotypes in general and summarise current knowledge regarding RB1-deficient cutaneous carcinomas, highlighting the potential uses of RB1 pathway characterisation for diagnosis, prognosis and therapeutic purposes.

To therapeutically target the CR factors, we used histone deacetylase (HDAC) inhibitors to collapse the chromatin architecture and induce topological blurring of superenhancer loops, abrogating core TF expression and halting tumor growth. To our knowledge, our study presents the first example of oncogenic cross-regulation between viral and human epigenomic circuitry to generate interlocking and essential transcriptional feedback circuits that explain why MCPyV causes neuroendocrine cancer and represent a tumor dependency that can be targeted therapeutically.

In this review, we present the current therapeutic opportunities and future directions of immunotherapy in the management of malignant melanoma, cutaneous squamous cell carcinoma, basal cell carcinoma, and Merkel cell carcinoma, accompanied by a brief overview of their mechanisms of action. Ambrus L, Balatoni T. Immunotherapy of cutaneous neoplasms.

The optimal cost-effective panel is POU4F3 with keratin AE1/AE3 or pan-keratin, which achieves 100% sensitivity while reducing reliance on less effective stains. Adoption of this focused IHC panel may serve to standardize SLN evaluation for MCC and improve diagnostic accuracy and efficiency.

In summary, we expand upon descriptions of H3K27me3 labeling in MCC and characterize patterns of H3K27me3 in other tumor types including small cell carcinomas and olfactory neuroblastoma. Our findings support diagnostic utility for the widely available marker H3K27me3 in MCC, with weaker labeling favoring MCC over mimics in challenging cases.

P1/2, N=7, Active, not recruiting, Sotio Biotech Inc. | Trial primary completion date: Oct 2027 --> Oct 2025

P1, N=56, Recruiting, Memorial Sloan Kettering Cancer Center | Active, not recruiting --> Recruiting

Cells were then subjected to combined treatment with inhibitors and cisplatin (CDDP), and viability and ROS levels were further analyzed. Our results clearly illustrate that cells treated with NNMT inhibitors underwent significant reductions in viability, increased ROS production and activation of apoptotic pathways. Given the association of NNMT with cancer aggressiveness, inhibiting its catalytic activity might present a novel strategy for counteracting cancer growth and chemoresistance, providing the rationale for an effective anti-cancer therapy based on the use of specific NNMT inhibitors.

Despite not containing a consensus E2 site, we detected weak E2F binding to the NCCRs of BKPyV and SV40, suggesting that E2Fs also contribute to transcription of their early genes. Overall, our findings challenge the existing paradigm of PyV infection, that LT expression activates E2F signaling via RB1 inhibition, and suggest that E2Fs must already be active in the PyV-infected host cell for LT/ST expression and viral replication.

This region appears to be critical for helping the virus maintain latency by fine-tuning the host's response. Our findings provide new insight into how MCPyV may regulate early infection dynamics and suggest that identifying functional domains such as LIT could help guide future approaches to study viral persistence and its contribution to MCC.

P1/2, N=31, Terminated, Transgene | N=48 --> 31 | Trial completion date: Apr 2025 --> Oct 2025 | Recruiting --> Terminated | Trial primary completion date: Apr 2025 --> Oct 2025; Sponsor decision following completion of Phase I part not driven by safety reason