Squamous Cell Skin Cancer

P2, N=22, Not yet recruiting, University of Michigan Rogel Cancer Center | Trial completion date: Dec 2029 --> Mar 2030 | Initiation date: Dec 2024 --> Mar 2025 | Trial primary completion date: Dec 2027 --> Mar 2028

P2, N=24, Recruiting, M.D. Anderson Cancer Center | Not yet recruiting --> Recruiting

P1/2, N=46, Terminated, Sanofi | Active, not recruiting --> Terminated; Early discontinuation based on strategic sponsor decision not driven by any safety concerns

Erastin was applied to induce ferroptosis...M2 exosomes-derived circ_0088494 recruited KMT2D to promote H3K4me1 modification of STEAP3, thereby inhibiting ferroptosis in cSCC. This study might provide a novel target for cSCC treatment.

Finally, we discuss the implications for future cSCC management and highlight areas for further research. As molecular profiling techniques continue to evolve, GEP represents a promising approach to optimizing care for cSCC patients, aligning with the growing emphasis on personalized medicine in oncology.

TMB-high (≥10 mut/Mb) was observed in 27% (n = 41) of the patients, with a median age of 75 years for this group. TMB-low (<10 mut/Mb) was observed in 73% (n = 111) of the patients; their median age was 67 years.

P2, N=166, Terminated, SOTIO Biotech AG | Active, not recruiting --> Terminated; Due to lack of expected efficacy shown at the time of the interim analysis

P1, N=18, Recruiting, University of Southern California | Trial completion date: Jan 2026 --> Jan 2027 | Trial primary completion date: Jan 2025 --> Jan 2026

This study suggests that immunotherapy is less beneficial in SCC-MU. More work is needed to verify our findings and explore other treatment options.

This finding explains, in part, the molecular mechanism of CSCC. Investigative approaches focused on suppressing miR-31 or enhancing RhoBTB1 signaling pathways are promising avenues for developing targeted therapies for CSCC.

P2, N=25, Recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial primary completion date: Jul 2025 --> Oct 2025

P1, N=7, Active, not recruiting, National Cancer Institute (NCI) | N=37 --> 7 | Trial completion date: Nov 2024 --> Dec 2025

P2, N=44, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025

Lenalidomide, a derivative of thalidomide, is a type of immunomodulatory drug (IMiD) that has been standard therapy for multiple myeloma (MM) and other hematologic malignancies for almost two decades. In addition, treatment with IMiDs is also associated with an increased risk for myelodysplastic neoplasms (MDS), squamous cell carcinoma of the skin, and, less frequently, acute lymphoblastic leukemia (ALL). We present a case of an elderly male with MM and multiple subsequent skin cancers, who presented with pancytopenia and was diagnosed with B-lymphoblastic leukemia (B-ALL) after 10 years of maintenance lenalidomide therapy.

Radiation therapy was administered, which improved leukocytosis and decreased G-CSF and PTHrP levels. Through a case report and literature review, we explored the clinical characteristics of tumors that produce G-CSF and PTHrP.

MNP@CD26@17D-mediated ferroptosis might be executed by ferritinophagy as judged by elevated levels of the ferritinophagy marker NCOA4 and a decreased pool of ferritin. As 24 h treatment with MNP@CD26@17D did not induce hemolysis in human erythrocytes in vitro, this newly designed nanoplatform could be considered as an optimal multifunctional tool to target and eliminate senescent cells of skin origin, overcoming their apoptosis resistance.

P3, N=450, Active, not recruiting, Merck Sharp & Dohme LLC | Trial completion date: Sep 2028 --> Dec 2025

Clinical trials that studied the combination of the first generation BTKi ibrutinib and V have shown the feasibility and efficacy of the regimen. Given the favorable safety profile and sustained efficacy of acalabrutinib, combination regimens with venetoclax without (AV) or with obinutuzumab [O] (AVO) have been studied in the first line setting, and favorable efficacy and safety have been reported...Patients with significant cardiovascular disease, absorption issues, active bleeding or history of bleeding diathesis or required/currently receiving anticoagulation with warfarin or equivalent vitamin K antagonists were excluded...Clinical responses including uMRD4 at the end of treatment and the safety profile will be assessed. The trial is actively enrolling at Fred Hutchinson Cancer Center/University of Washington.

P1, N=25, Recruiting, Dana-Farber Cancer Institute | Not yet recruiting --> Recruiting

P2, N=98, Not yet recruiting, NRG Oncology | Trial completion date: Sep 2026 --> Jan 2027 | Initiation date: Oct 2024 --> Apr 2025 | Trial primary completion date: Sep 2026 --> Jan 2027

We hypothesize that this reaction was triggered by azathioprine dose reduction. Dose modification of long-term immunosuppressive medications in patients with a transplantation history who later develop SCCs warrants further investigation.

Mesenchymal features were associated with a higher metastatic capacity and anoikis resistance, yet this comes with a sensitivity toward TNF-induced cell death. Altogether we provide insights in cSCC heterogeneity and modes to target mesenchymal-metastasis inducing cells.

P3, N=266, Not yet recruiting, Centre Leon Berard

P2, N=77, Terminated, Regeneron Pharmaceuticals | Active, not recruiting --> Terminated; Sponsor Decision related to study drug supply

P2, N=34, Recruiting, University of Southern California | Trial completion date: Jun 2025 --> Jun 2026 | Trial primary completion date: Jun 2024 --> Jun 2025

We generated tamoxifen inducible Dab2 conditional knockout system for our study...In patients, TCGA data analysis of skin cancer melanoma (SKCM) showed a trend where high levels of Dab2 correlated with poor overall survival. The present study shows that Dab2 promotes tumour progression in skin SCC.

Notably, our study showed that proteomes sampled with e-biopsy from cSCC and BCC lesions are different and that proteins of CRNN, SULT1E1, and ITPK1 genes are significantly overexpressed in BCC in comparison with those in cSCC. Our results provide evidence that the e-biopsy approach could potentially be used as a tool to support cutaneous lesions classification with molecular pathology.

Overall, muSCC shows similar genomic alterations and TMB to HPV(–) vSCCs. CGP of inflammation-associated SCCs may be important to more fully inform therapeutic options and stratification in clinical trials.

Cemiplimab is a safe and effective therapy, particularly in elderly patients. Well-differentiated tumors with low proliferative index, intratumoral inflammatory infiltrate, and tumor necrosis may predict better clinical response.

Following initiation of standard chemotherapy agents, carboplatin and paclitaxel, the patient developed a diffuse, itchy rash over her abdomen, back, and bilateral upper and lower extremities. Biopsy of the rash revealed a diffuse non-resectable cutaneous squamous cell skin carcinoma (cSCC) in situ. Consequently, a PD1-inhibitor was added to her neoadjuvant chemotherapy regimen, which resulted in complete response to both metastatic ovarian and diffuse cSCC in situ at time of surgery.

P1, N=182, Active, not recruiting, Incyte Corporation | Trial completion date: Oct 2025 --> Dec 2024 | Trial primary completion date: Jul 2025 --> Aug 2024

In conclusion, we have identified CCNA2, CCNB2, and UBE2C as novel biomarkers for cSCC, and the NEAT1/H19-hsa-miR-148a-3p-CCNA2 and NEAT1-hsa-miR-140-3p-UBE2C ceRNA networks may represent molecular mechanisms under-lying cSCC progression. The findings of this study offer new diagnostic and therapeutic options for cSCC patients.

P1/2, N=188, Active, not recruiting, Ascendis Pharma Oncology Division A/S | Recruiting --> Active, not recruiting

P1, N=25, Not yet recruiting, Dana-Farber Cancer Institute

This review will provide an overview of our current understanding of FGFR2 and potential mechanisms in which we can target FGFR2 in cSCC. The goals of this review are the following: (1) to highlight our current knowledge of the role of FGFR2 in healthy skin and contrast this with its role in the development of cancer; (2) to further explain the specific molecular mechanisms that FGFR2 uses to promote tumorigenesis; (3) to describe how FGFR2 contributes to more invasive disease; (4) to describe its immunosuppressive effects in skin; and (5) to evaluate its effect on current anticancer therapy and discuss therapies on the horizon to target FGFR2 related malignancy.

Among these, we further validated LINC00704 and LINC01116 as proliferation-regulating lncRNAs in cSCC lines and potential biomarkers of cSCC progression. Taken together, our study provides a comprehensive signature of lncRNAs with roles in regulating cSCC progression.

P=N/A, N=118, Not yet recruiting, Emory University

P=N/A, N=60, Active, not recruiting, King's College London

In contrast, the SKH-hr1 mice were found to be the least suitable, even though they are albino. Notably, proteasome analysis revealed a potential role of proteasome activity in squamous cell carcinogenesis.

P=N/A, N=20, Recruiting, University of Wisconsin, Madison | Not yet recruiting --> Recruiting

P=N/A, N=115, Not yet recruiting, Skin Analytics Limited

This may be the signature of genuine parotid primary SCC, but metastasis from an SCC from another organ cannot be excluded. Accordingly, a diagnosis of primary parotid gland SCC should be viewed with skepticism.