Squamous Cell Skin Cancer

P=N/A, N=90, Recruiting, Sunshine Coast University Hospital | Not yet recruiting --> Recruiting

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.

This report conducts a systematic review of four principal studies: ① The KEYNOTE-689 trial was the inaugural study to establish that "pembrolizumab combined with standard therapy" diminishes the risk of disease progression or mortality by 34% in patients with Programmed Cell Death-L1(PD-L1) CPS ≥ 10, resulting in Food and Drug Administration (FDA) approval; ② The NIVOPOSTOP trial revealed that adjuvant nivolumab alongside CRT significantly improved 3-year disease-free survival (DFS) (63.1% vs. 52.5%), with efficacy unaffected by PD-L1 status; ③ The C-POST trial indicated a substantial DFS advantage with adjuvant cemiplimab in high-risk skin squamous cell carcinoma (HR = 0.32);④ The NeoRTPC02 trial innovatively integrated low-dose radiotherapy with immune chemotherapy, achieving a pathological complete response(pCR) rate of 60.9%. Nonetheless, the ideal treatment approach, strategies for reducing radiation dosage, preservation of organ function, and selection of biomarkers necessitate additional confirmation. Future efforts must focus on interdisciplinary collaboration to enhance tailored precision treatment protocols, aiming to improve the 5-year survival rate of HNSCC while maintaining organ function and quality of life.

From the high rate of poor outcomes evident in our series, we propose that wide local excision, postoperative adjuvant radiotherapy and follow-up imaging surveillance are justified. However, further studies are now required to better establish treatment guidelines for this rare aggressive adnexal tumour.

We integrate data on epidermal growth factor receptor inhibitors, phosphoinositide-3-kinase inhibitors, taxanes such as docetaxel, fluoropyrimidines such as capecitabine, immune checkpoint inhibitors, BRAF and MEK inhibitors, mechanistic target of rapamycin inhibitors, Bruton tyrosine kinase inhibitors and chimeric antigen receptor T-cell therapy. We highlight the vulnerability of older adults, in whom age-related skin changes, comorbidities and polypharmacy amplify the impact of these events while evidence from dedicated prospective studies remains scarce. The review synthesizes practical, mechanism-oriented strategies for prevention and stepwise management, from basic skin care and photoprotection to targeted use of antibiotics, corticosteroids and treatment modification, with the goal of supporting timely recognition of cutaneous toxicity and multidisciplinary care that preserves both quality of life and the anticancer efficacy of therapy.

Furthermore, loss of FTO reduced tumor growth in mice and FTO expression was upregulated in cutaneous squamous cell carcinoma (cSCC) compared with normal skin. Together, these findings uncover a critical role for FTO in regulating post-transcriptional gene expression in the UVB damage response and suggest that FTO may be a therapeutic target in skin cancer.

P2, N=44, Recruiting, National Cancer Institute (NCI) | Not yet recruiting --> Recruiting | Initiation date: Nov 2025 --> Aug 2026

In conclusion, this study identifies ROR1 as a novel marker of aggressive cSCC, linked to poor differentiation, lymphatic spread and perineural invasion. ROR1 holds potential both as a prognostic biomarker and as a therapeutic target, encouraging future exploration of ROR1-directed therapies in advanced cSCC.

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.