Squamous Cell Skin Cancer

Analysis of human specimens further demonstrated progressive upregulation of PDPN and CLEC-2 expression during the transition from normal skin to AK and cutaneous squamous cell carcinoma (cSCC). Collectively, our findings identify a PDPN-CLEC-2-mediated stromal remodeling program that links UVB-induced oxidative stress to malignant transformation in AK and highlight this signaling axis as a potential therapeutic target for photochemoprevention.

P1, N=4, Active, not recruiting, Ohio State University Comprehensive Cancer Center | Recruiting --> Active, not recruiting | N=40 --> 4 | Trial primary completion date: Dec 2026 --> Apr 2026

P1, N=0, Withdrawn, Ankyra Therapeutics, Inc | N=20 --> 0 | Not yet recruiting --> Withdrawn

P=N/A, N=119, Completed, University Hospital, Bordeaux | Recruiting --> Completed | N=200 --> 119

P=N/A, N=70, Recruiting, University Hospital, Angers | Not yet recruiting --> Recruiting

Drug prediction and docking identified camptothecin, hydroquinone, and resveratrol with favorable binding (e.g., HIF1A-camptothecin -8.7 kcal/mol; GSTP1-camptothecin -8.6 kcal/mol)...Keratinocyte pseudotime revealed progression from normal to metastatic states with concordant keratinocyte‑related gene programs. HIF1A and GSTP1 are promising diagnostic biomarkers for cSCC, linked to altered immune landscapes, enhanced intercellular signaling, and potential druggable interactions.

P=N/A, N=28, Recruiting, Alpha Tau Medical LTD. | Not yet recruiting --> Recruiting | Trial primary completion date: Dec 2025 --> Dec 2026

P=N/A, N=86, Active, not recruiting, Alpha Tau Medical LTD. | Recruiting --> Active, not recruiting | Trial completion date: Dec 2025 --> Apr 2027 | Trial primary completion date: Dec 2025 --> Apr 2027

Dendritic cells shifted from early inflammatory antigen-presenting programs toward late PD-L1 / IFN -regulatory states; macrophages showed monotonically increasing TLR4 -associated myeloid activation; and T cells defined a "hot but exhausted" microenvironment in established cSCC. These findings identify SD and AK as biologically active stages for topical immunoprevention and provide a cellular roadmap for PD-L1 / PD-1 and TLR4 blockade strategies.

Our findings demonstrate that Bcl-2 promotes cSCC progression by modulating MAMs structure and function to inhibit p53-mediated mitochondrial apoptosis. The study identifies the novel Bcl-2-MAMs-p53 signaling axis that plays a pivotal role in determining cSCC cell fate, highlighting a promising target for therapeutic intervention.