Squamous Cell Skin Cancer

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

Our findings show that the manipulation of UV-induced Tregs prevents early cSCC establishment. Thus, strategies aimed at modulating Treg function or abundance in the skin may represent a feasible therapeutic avenue for the prevention of cSCC tumor emergence in patients.

Building on this foundation, the potential clinical value of immune checkpoint inhibitors (cemiplimab, pembrolizumab) in treating advanced cSCC is summarized based on data from relevant clinical trials. This review is distinguished from general tumor immunotherapy reviews by offering dedicated references for cSCC precision immunotherapy. In addition, priority is emphasized for future investigations into combination therapy regimens and the development of personalized tumor vaccines.

Surprisingly, actinic keratoses are often not related to their neighboring cSCC. Spatial analyses reveal gene expression heterogeneity, including checkpoint molecule enrichment at invasive fronts, highlighting tumor and immune cell interactions.

Cemiplimab and pembrolizumab are now established systemic therapies, producing durable responses in a proportion of patients. This review summarizes current evidence on the management of advanced cSCC in high-risk and underserved patient groups, integrating trial data, real-world evidence, and contemporary guidelines. It also highlights key gaps in knowledge and outlines future directions, with particular focus on the interplay between host immune status, tumor biology, and therapeutic response.

P2, N=44, Not yet recruiting, National Cancer Institute (NCI) | Trial completion date: May 2027 --> Nov 2027 | Trial primary completion date: May 2027 --> Nov 2027

P2, N=28, Recruiting, University of Michigan Rogel Cancer Center | Not yet recruiting --> Recruiting

This study highlights the power of NGS in diagnosing genetically distinct disorders without shared pathogenic mechanisms within a single family. Our findings underscore the clinical value of comprehensive genomic sequencing for unravelling complex hereditary conditions, especially when multiple rare disorders segregate independently in kindreds.

In vivo, MF effectively suppressed cSCC growth without causing organ toxicity. In conclusion, MF inhibits cSCC progression both in vitro and in vivo with minimal toxicity, primarily through targeting HSP90α and activating the ROS/MAPK pathway.

P2, N=35, Active, not recruiting, University of Southern California | Suspended --> Active, not recruiting | Trial primary completion date: Jun 2026 --> Nov 2025

P2, N=21, Completed, Wake Forest University Health Sciences | Active, not recruiting --> Completed | Trial completion date: Feb 2026 --> Apr 2025

Our findings provide a comprehensive cellular atlas of CSCC, highlighting the association of CAFs in HPV infection and tumor progression of CSCC. These results also offer potential diagnostic and prognostic biomarkers for CSCC patients.