Squamous Cell Skin Cancer

The management of adverse events and toxicities in molecular-targeted therapies is crucial and requires careful monitoring and control. The paper further discusses future directions for therapeutic advancement and research in this area, as well as the difficulties and constraints associated with conventional therapies.

Multimarker combination defined CAF subset, PDGFRα-/PDGFRβ+/FAP+, was associated with invasion and metastasis, and independently predicted poor disease-specific survival. These results identify high PDGFRβ expression alone and multimarker combination PDGFRα-/PDGFRβ+/FAP+ by CAFs as potential biomarkers for risk of metastasis and poor prognosis.

These evidences suggest the protective effect of CAP in CSCC, and CAP has the potential clinical application of CSCC.

P2/3, N=1012, Recruiting, Merck Sharp & Dohme LLC | Not yet recruiting --> Recruiting

Here we report a case of radiation-induced cSCC with a high level of tumor-mutation burden that developed in a patient with MF who was successfully treated with pembrolizumab. The present case suggests that pembrolizumab might be an optimal therapy for radiation-induced cSCC, even at advanced stages.

The THOC7-AS1/OCT1/FSTL1 axis regulates EMT and promotes tumor progression in cSCC. This study provides clues and ideas for cSCC targeted therapy.

P3, N=430, Active, not recruiting, Merck Sharp & Dohme LLC | Recruiting --> Active, not recruiting

Mutations in genes associated with ultraviolet light (UV) signature were most frequently encountered (SBS7b = 74% and SBS7a = 72%), with higher prevalence in the ETH cohort, whereas SBS2 and SBS13 signatures were more common among MDA HPV+ conjSCCs. Our findings suggest that UV exposure may play a major role in conjSCC, with a higher prevalence in the ETH cohort compared with the MDA cohort, where HPV also contributes.

In conclusion, ATP citrate lyase may serve as a tumour biomarker. It is highly expressed in cutaneous squamous cell carcinoma and may serve as a therapeutic target.

P=N/A, N=0, Withdrawn, Ohio State University Comprehensive Cancer Center | N=40 --> 0 | Suspended --> Withdrawn

Furthermore, our findings suggested that NEDD4L can interact with GP130 and promote its ubiquitination in skin tumors. In conclusion, our results indicate that NEDD4L could act as a tumor suppressor in skin cancer, and inhibition of GP130 could be a potential therapeutic method for treating this disease.

P2, N=225, Suspended, Regeneron Pharmaceuticals | Recruiting --> Suspended

P2, N=49, Completed, M.D. Anderson Cancer Center | Active, not recruiting --> Completed | N=71 --> 49 | Trial completion date: Jan 2025 --> Apr 2024 | Trial primary completion date: Jan 2025 --> Apr 2024

P1, N=824, Recruiting, Seagen Inc. | Trial completion date: Oct 2024 --> Oct 2028 | Trial primary completion date: Jul 2024 --> Nov 2026

The HCB-541 cells exhibited high phosphorylated levels of EGFR, AXL, Tie, FGFR, and ROR2, and high sensitivity to cisplatin, carboplatin, and EGFR inhibitors. Our study successfully established HCB-541, a new cSCC cell line that could be useful as a valuable biological model for understanding the biology and therapy of metastatic skin cancer.

The immunoreactivity to the investigated markers confirms the multistage skin carcinogenesis, and their involvement starting from the initiation phase of the cancer process. The importance of the studied markers in the evolution and prognosis of precancerous lesions of CSCC is also supported by the linear correlations revealed between the immunoexpressions of P16, Ki67 and the membranous immunoexpression of Beta-catenin in AK.

Decreased expression of SIRT6 can inhibit the occurrence and development of CSCC.

This cohort study of patients who were treated with neoadjuvant cemiplimab or pembrolizumab for advanced cSCC from January 2018 to January 2023 was conducted at 2 academic institutions in Boston, Massachusetts. Outside of clinical trials, it is not infrequent for patients to opt out of surgery for regressing tumors. The inclusion of higher-risk patients and preference for nonsurgical treatment are 2 factors that might explain the numerically lower pathologic response rate in this institutional experience.

The proposed variants were not associated with cSCC risk in this Mexican population, but we recognize the need for analyzing larger population groups to elucidate the disease-causing role of rare variants.

The expression of E-cadherin was increased, while the expression of snail, β-catenin, p-AKT, p-S6 and p-4EBP1were decreased. Conclusion YAP is highly expressed in cSCC tissues, and promotes the cell migration and invasion of cSCC cells by activating the PI3K/AKT signaling pathway and EMT.

P=N/A, N=300, Active, not recruiting, Queen Mary University of London

ART guidance is not determined by the presence of specific clinicopathologic factors, with treated and untreated patients sharing the same risk factor profiles. cSCC risk determination based on NCCN recommendations for clinical factor assessment results in inconsistent use of ART. Including tumor biology-based prognostic information from the 40-GEP refines risk and identifies patients who are most appropriate and likely to benefit from ART, and those that can consider deferring ART.

However, the 40-GEP classified 70% of tumors missed by the nomogram as high-risk Class 2. These data demonstrate that 40-GEP improves risk stratification of NCCN high or very high-risk patients who were categorized as low-risk by this nomogram.

P1, N=35, Completed, Rahul Aggarwal | Active, not recruiting --> Completed | Phase classification: P1b --> P1

P2, N=30, Active, not recruiting, Diwakar Davar | Recruiting --> Active, not recruiting

P=N/A, N=470, Recruiting, Johns Hopkins University | Not yet recruiting --> Recruiting

P1/2, N=75, Terminated, Merck Sharp & Dohme LLC | Phase classification: P1b/2 --> P1/2 | Completed --> Terminated; Business Reasons

The panel identified gaps in clinical practice in which 40-GEP testing has particular utility: in escalation of care for lower-stage patients with high-risk tumors; in de-escalation of care for patients for whom the risks of ART may outweigh the benefits; and in decision-making regarding elective radiation to the nodal basin. The expert panel developed a risk-based clinical workflow for ART in patients with cSCC, utilizing 40-GEP testing within NCCN management guidelines and AJCC-8 staging.

Herein, we developed a strategy using the combination of PDT and hypoxia-activated bioreductive drug tirapazamine (TPZ)...With laser irradiation, overexpressions of PDT tolerance factors NQO1 and HIF-1α were inhibited by this PDT process. The synergistic effect of PDT and TPZ significantly improved the performance of DPTC-MNs in the treatment of melanoma and cutaneous squamous cell carcinoma and has good biocompatibility.

In conclusion, this systematic review showed that NMSC-derived EVs display promise as therapeutic targets and diagnostic biomarkers. Further research is imperative to fully comprehend EV mechanisms and explore their potential in cancer diagnosis and treatment.

P2, N=180, Not yet recruiting, ECOG-ACRIN Cancer Research Group | Initiation date: Jan 2024 --> Apr 2024

P2, N=50, Recruiting, Mayo Clinic | Not yet recruiting --> Recruiting

One of the proposed mechanisms associated with this tumor resistance has been the accumulation of high-molecular-weight hyaluronic acid (HMWHA) in the epidermis. Researchers were able to conclude that the CD44/HMWHA interaction mediates cancer cell apoptosis and restricts cell cycle progression as a mechanism of cancer resistance in naked mole rats.

P2, N=320, Active, not recruiting, SOTIO Biotech AG | Recruiting --> Active, not recruiting | Trial primary completion date: Sep 2023 --> Apr 2025

This topical regimen consisted of tazarotene cream, imiquimod cream, and 5-fluorouracil solution, applied for 30 days. This case marks the first recorded instance of successful topical medical treatment of AFX, offering an alternative for patients who may opt out of surgical intervention. Continued research to assess the broader efficacy of this approach is encouraged.

P1, N=200, Active, not recruiting, SOTIO Biotech AG | Trial completion date: Dec 2023 --> Nov 2024 | Trial primary completion date: Dec 2023 --> Aug 2024

P2/3, N=1012, Not yet recruiting, Merck Sharp & Dohme LLC

P1, N=77, Terminated, Sanofi | Completed --> Terminated; Sponsor terminated the study for non-safety reasons

Finally, the repression of β-catenin by miR-184, inhibits the neoplastic phenotype of SCC cells. Taken together, miR-184 behaves as an epidermal tumor suppressor, and may provide a potentially useful target for skin SCC therapy.

P2, N=20, Not yet recruiting, Melanoma Institute Australia

P1, N=77, Completed, Sanofi | Active, not recruiting --> Completed

The 40-GEP test demonstrates accurate, independent, clinically actionable stratification of metastatic risk and improves predictive accuracy when integrated into risk classification systems. The improved accuracy of risk assessment when including tumor biology via the 40-GEP test ensures more risk-aligned, personalized patient management decisions.