Skin Cancer

They discovered unique T cell epitopes and used the power of bar-coded tetramers to portray immune checkpoint inhibitor-induced immunogenicity as a predictor of clinical response. These findings provide the foundation for therapeutic possibilities for MCC, including vaccines and adoptive T cell- and T cell receptor-driven (TCR-driven) treatments.

These T cells provided strong tumor-rejection capacity while retaining a favorable phenotype for adoptive cell transfer. These findings demonstrate that T-Ag-specific T cells are associated with the clinical outcome to PD-1 blockade and that Ag-presenting scaffolds can be used to boost such responses.

P=N/A, N=65, Completed, Enspectra Health | Trial primary completion date: Dec 2022 --> Aug 2023

P1, N=215, Active, not recruiting, Eli Lilly and Company | Trial completion date: Mar 2024 --> Jul 2024

Malignant melanomas (17.24%) are the extremely common cutaneous tumors diagnosed in this study. Meanwhile, benign tumors such as trichilemmoma, trichoepithelioma, pilomatricoma, and paraganglioma are less frequent in dogs.

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

Our results give novel insights into the remodeling of the myeloid landscape by tumor-targeted therapy. We demonstrate that the transient immunogenic tumor milieu contains more activated DC. This knowledge has important implications for the development of future combinatorial therapies.

The localization of the tumors in the area of the UV-exposed sites within the potential/actual contamination of the 4 preparations (simultaneously) in the described patient are indicative of a possible pathogenetic influence in the context of the already mentioned Nitroso-(Photo)carcinogenesis. Polycontamination of polymedication remains a so far unresolvable problem.

The presented data are confirmatory with respect to previously published scientific observations on the carcinogenic effects of valsartan, candesartan, bisoprolol, metoprolol, perindopril, lisinopril and amlodipine. The thesis of the controlled spread of cancer sounds more than logical today because: whoever controls and regulates the spread of carcinogens/mutagens/nitrosamines is also able to control the occurrence and spread of skin cancer. The Pharmaco-oncogenesis of skin cancer is determined by exogenously mediated Nitrosogenesis or the permissive availability for certain nitrosamines in drugs worldwide.

Once again, we present a patient who took the antiarrhythmic (nitroso-) drug propafenone and developed a relatively short-term nodular melanoma with a subsequent fatal outcome. We comment on the role of drug-mediated nitrosogenesis and its relationship to photocarcinogenesis and onco-pharmacogenesis.

P2, N=18, Recruiting, Weill Medical College of Cornell University | Trial completion date: Feb 2025 --> Sep 2026 | Trial primary completion date: Feb 2024 --> Sep 2026

P=N/A, N=80, Enrolling by invitation, OHSU Knight Cancer Institute | Trial completion date: Jun 2024 --> Dec 2024

P2, N=56, Recruiting, National Cancer Institute (NCI) | Not yet recruiting --> Recruiting

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

The 5-year benefit-risk profile for upadacitinib in RA remains favorable.

The masses were diagnosed as Langerhans cell histiocytosis. Congenital cutaneous Langerhans cell histiocytosis has not been reported previously in cattle, to our knowledge, and should be included in the differential diagnosis of congenital nodular skin lesions.

P2, N=132, Recruiting, Melanoma and Skin Cancer Trials Limited | Trial completion date: Dec 2028 --> Apr 2028 | Trial primary completion date: Dec 2025 --> Apr 2027

These findings establish a preclinical foundation for the combined use of an anti-HER2 drug conjugate and a BRAF inhibitor in the treatment of BRAF-mutant cutaneous melanoma.

Genomic deletions are also detected in tumor samples from melanoma and breast cancer patients expressing altBRAFs. Along with the identification of altBRAFs in BRAF wild-type and in MAPKi-naive melanoma samples, our results represent a major shift in our understanding of mechanisms leading to the generation of BRAF transcripts variants associated with resistance in melanoma.

The search for restricted antitumoral responses without graft rejection is of paramount importance. This review summarizes the current knowledge of the use of ICI in KTR, the potential mechanisms involved in kidney graft rejection during ICI treatment, potential biomarkers of rejection, and how to deal with rejection in clinical practice.

P1, N=7, Completed, Claire Verschraegen | Active, not recruiting --> Completed

P1/2, N=126, Not yet recruiting, 7 Hills Pharma, LLC

P2, N=80, Recruiting, ImaginAb, Inc. | Phase classification: P2b --> P2 | Trial completion date: Dec 2025 --> Jul 2025 | Trial primary completion date: Dec 2024 --> Jul 2025

P2, N=19, Completed, Memorial Sloan Kettering Cancer Center | Active, not recruiting --> Completed | Trial completion date: Jun 2024 --> Feb 2024 | Trial primary completion date: Jun 2024 --> Feb 2024

GLUT1 is upregulated even during the preinvasive phase in patients with invasive EMPD, suggesting that GLUT1 immunostaining can predict the risk of dermal invasion. The present study provides novel evidence to pursue in vitro and in vivo studies to confirm that upregulated expression of GLUT1 enhances tumor aggressiveness in EMPD.

P2, N=35, Active, not recruiting, National Cancer Institute (NCI)

Our study illustrates that the tumor immune microenvironment prior to CPI treatment can be indicative of response. In perspective, modulating the myeloid and/or effector cell compartment by altering the described cell interactions and transitions could improve immunotherapy response.

Here, we established a novel prognostic model for melanoma, which showed promising predictive performance and may serve as a biomarker for the efficacy of immune checkpoint inhibition therapy in melanoma patients. In addition, we explored the function of two genes in the model in melanoma.

Dupilumab use is associated with an increased risk of CTCL in patients with AD in this cohort.

Our findings highlight the reliability of TIPRGPI as a prognostic signature and its potential application in risk classification, immunotherapy response prediction, and drug candidate identification for melanoma treatment. The "TIP genes" guided strategy presented in this study may have implications beyond melanoma and could be applied to other cancer types.

Interestingly, RNAseq data in the Human Protein Atlas give support for a possible role of NR4A3 because it is particularly upregulated in human skin cancer, and it belongs to a cluster of genes associated with skin cancer and melanin biosynthesis. The Grey mutation and its association with melanoma provide a possibility to study the path to tumour development in numerous Grey horses carrying exactly the same predisposing mutation.

Furthermore, we conducted experiments on A375 and WM-115 cells to validate the function of PPP2R1A, a pivotal gene within the LRS. Our comprehensive approach, combining advanced bioinformatics analyses with an extensive review of current literature, presents compelling evidence regarding the significance of LDL within the cutaneous melanoma microenvironment.

P=N/A, N=0, Withdrawn, Johns Hopkins University | N=150 --> 0 | Trial completion date: Aug 2024 --> Dec 2025 | Not yet recruiting --> Withdrawn | Trial primary completion date: Jun 2024 --> Dec 2025

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.

P=N/A, N=324, Not yet recruiting, Mayo Clinic

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

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

P=N/A, N=100, Recruiting, OHSU Knight Cancer Institute | Trial completion date: Dec 2024 --> Dec 2026 | Trial primary completion date: May 2024 --> May 2026

The histologic features of CSM present a unique set of challenges posing a diagnostic dilemma, as they can bear resemblance to a range of benign and malignant cutaneous neoplasms including ALK-negative epithelioid cell histiocytoma, epithelioid perineurioma, malignant or nevoid melanoma, and epithelioid sarcoma. An accurate diagnosis is crucial for guiding proper clinical management considering that this entity typically demonstrates an excellent prognosis following a complete surgical excision.

Flow cytometry revealed alterations in cell cycle distribution, increased apoptosis and significantly inhibition of cell survival. L-kynurenine and quinolinic acid are exogenous kynurenine compounds which inhibited cell survival through extracellular signal-regulated protein kinase inhibition, induced cell cycle alterations and induced apoptosis in B16 F10 melanoma cells.

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.

Moreover, we found that NADPH oxidase (NOX)-dependent generation of ROS was responsible for AKT activation and oxidative DNA damage repair downstream of varMC1R. These observations provide a better understanding of the functional properties of melanoma-associated MC1R alleles and may be useful for the rational development of strategies to correct defective varMC1R responses for efficient photoprotection and melanoma prevention in fair-skinned individuals.