Squamous Cell Skin Cancer

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.

Neoantigens with features shared with validated immunogenic neoantigens were decreased in clonal relative to subclonal cancer cell populations in high-immune-infiltrate tumors from immunocompetent patients. Thus, the immune system restricts cancer cells expressing immunogenic antigens from clonal populations in primary, treatment-naive human tumors.

Collectively, our findings identify CD70 as a stress-inducible signaling hub that links DNA damage, inflammation, and tumor-stromal communication in skin carcinogenesis. Targeting CD70 may disrupt this feed-forward inflammatory circuit and provide a therapeutic strategy for UV-driven and inflammation-associated cSCC.

Enhancer of zeste homologue 2 overexpression was noted in cutaneous squamous cell carcinoma cases, indicating that enhancer of zeste homologue 2 had a potential role in cutaneous squamous cell carcinoma tumourigenesis.

P1, N=85, Terminated, Boundless Bio, Inc. | Trial completion date: Mar 2027 --> Mar 2026 | Active, not recruiting --> Terminated | Trial primary completion date: Sep 2026 --> Mar 2026; Decision was made to halt the study based on overall clinical experience and market considerations. This decision was not driven by any safety signal.

P1, N=39, Recruiting, National Cancer Institute (NCI) | Initiation date: Jun 2026 --> Feb 2027 | Not yet recruiting --> Recruiting

Relying exclusively on clinicopathologic factors has limitations, contributing to inconsistent use of ART in clinical settings. This systematic review highlights that the 40-GEP test improves risk stratification in cSCC and aids in making more precise ART decisions, including determining which patients may safely defer treatment.

P2, N=35, Active, not recruiting, University of Southern California | Trial completion date: Jun 2027 --> Dec 2027 | Trial primary completion date: Nov 2025 --> Dec 2026