Skin Cancer

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

Nemvaleukin was well tolerated and demonstrated promising antitumor activity across heavily pretreated advanced solid tumors. Phase 2/3 studies of nemvaleukin are ongoing.

The Oral Rheumatoid Arthritis Trial Surveillance demonstrated an increased cancer risk among patients with rheumatoid arthritis (RA) taking tofacitinib compared with those taking tumor necrosis factor inhibitors (TNFis)...Of a total 27 661 drug exposures, drug initiations consisted of 20 586 TNFi exposures (74%), 2570 JAKi exposures (9%), 2255 abatacept exposures (8%), 1182 rituximab exposures (4%), and 1068 IL-6i exposures (4%)...Given the limitations of administrative claims data and confounding by indication, it is likely that these patients may have a higher disease burden, resulting in channeling bias. To better understand these associations, larger studies with longer follow-up time are needed.

How TPC2 activity is controlled in melanoma and the downstream molecular effects of TPC2 activation on melanoma development remain largely elusive. Here we show that the small GTPase Rab7a strongly enhances the activity of TPC2 and that effects of TPC2 on melanoma hallmarks, in vitro and in vivo strongly depend on the presence of Rab7a, which controls TPC2 activity to modulate GSK3β, β-Catenin, and MITF, a major regulator of melanoma development and progression.

P=N/A, N=30, Recruiting, Alpha Tau Medical LTD. | Trial completion date: Sep 2024 --> Sep 2026 | Trial primary completion date: Jun 2024 --> Jun 2025

Our findings underscore the importance of the cGAS-STING pathway in melanoma, presenting it as a critical target for enhancing anti-tumor immunity. By leveraging this pathway, future therapeutic strategies can potentially convert 'cold' tumors into 'hot' tumors, making them more susceptible to immune responses.

A dose escalation study in BALB/c mice showed that P-PENT and P-HEX were approximately 5-fold and 4-fold more tolerated than cisplatin, respectively. In conclusion, the present study provides evidence that P-PENT and P-HEX may have the characteristics of an effective and potentially safe anti-tumor drug that could be used in skin cancer treatment.

Finally, the in vivo proof-of-concept showed that the intratumoral administration of HAOA-AuNPs followed by three laser irradiations impaired tumor progression. Collectively, AuNP-based PTT holds significant potential to improve treatment efficacy and safety, offering a versatile and potent tool against cancer.

This study reveals changes in cell components in photoaged skin from a single case and provides novel insights into cellular subpopulations and pathology during repeated UVA-induced skin damage. These findings enhance our understanding of the complex interplay between different cells in photoaged skin and offer potential targets for preventing human skin photoaging and UV-induced skin cancers.

Our findings confirm the distinctive clinicopathological features of this very rare, recently described entity and expand its molecular genetic spectrum. Reflecting these findings, we propose modifying the name of this entity to "superficial neurocristic FET::ETS fusion tumor".

Therefore, melanoma tumor development was prevented by the overexpression of cell cycle inhibitors p16, p21, p27, and p53 due to UM + LunLip treatments. Since the topical application was effective, less invasive, and more practical for the user, this application will be recommended for future steps in in vivo studies.

There was a difference in immunohistochemical staining of HSP105 in basaloid skin tumors which helps in differential diagnosis. Differentiation between BCC, SCC, BSCC, MBCC, and BCC with squamous differentiation can be aided by immunohistochemistry using HSP105.

Overall, LAG-3 is expressed in MCC infiltrates and is prognostic in pre-immunotherapy MCC, suggesting a potential role for LAG-3 inhibition in MCC. Additionally, CD8 and γδ-T cells may play a critical role in the response to MCC, and γδ-T cell density may represent a novel biomarker in MCC.

Conversely, C-IKKα mice, whose keratinocytes are nearly devoid of endogenous nuclear IKKα, do not develop skin SCCs, although they exhibit hyperplastic skin with deficiencies in terminal epidermal differentiation, chronic cutaneous inflammation, and constitutive activation of STAT-3 and NF-κB signaling pathways. Altogether, our data demonstrate that alterations in the localization of IKKα in the nucleus or cytoplasm of keratinocytes cause opposite skin changes and differentially predispose to the growth of skin SCCs.

This meta-analysis supports the prognostic utility of the 31-GEP test in cutaneous melanoma prognostication. The test consistently stratified patients into clinically meaningful risk groups across multiple survival metrics. These findings support the potential clinical utility of the 31-GEP test in enhancing current staging systems and informing personalized management strategies for melanoma patients.

No abstract available

We identified SGK1, as a key downstream factor of Survivin, and its inhibition prevents BCC formation. This study uncovers the role and mechanisms by which Survivin regulates the competence of SCs to initiate BCC formation promoting the survival of oncogene-expressing SCs and self-renewing division while restricting differentiation and apoptosis.

P1, N=150, Recruiting, Invion Limited | Not yet recruiting --> Recruiting

P=N/A, N=156, Not yet recruiting, Pierre Fabre Medicament

Gedunin has been shown to promote melanoma cell death in vitro, suggesting that it could be used as a future treatment for malignant melanoma. Our findings suggested that GN might be applied as a preventative measure in the management of skin melanoma cells.

Treatment with recombinant OPN increased the expression of MMP-1 and inflammatory cytokines in human dermal fibroblasts and epidermal keratinocytes in vitro. Our results suggest that OPN may play a regulatory role in UV-induced skin inflammation.

In summary, targeted sequencing of a large NGS panel can detect predicted ultraviolet radiation mutational signatures in skin cancer with >99% specificity. This preliminary result warrants a potential application of mutational signature characterization in routine tumor profiling testing. Further investigation with larger data sets will follow up to determine the overall sensitivity and specificity for detection.

P1/2, N=19, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting | N=12 --> 19

P1, N=14, Active, not recruiting, H. Lee Moffitt Cancer Center and Research Institute | Recruiting --> Active, not recruiting

P=N/A, N=33, Not yet recruiting, Princess Alexandra Hospital

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

P2, N=26, Active, not recruiting, H. Lee Moffitt Cancer Center and Research Institute | Recruiting --> Active, not recruiting

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.

"BostonGene...announced the Company will present six posters at the Society for Immunotherapy of Cancer’s (SITC) 39th Annual Meeting taking place November 6-10, 2024 at the George R. Brown Convention Center in Houston, Texas. The research, conducted in collaboration with leading cancer centers, showcases the impact of BostonGene’s technology in advancing cancer treatment strategies, from deep molecular insights to predictive biomarkers."

P=NA | N=NA | "The study showed that integrating DecisionDx-Melanoma test results into SLNB decisions resulted in 25% fewer SLNBs performed compared to a matched patient cohort (p<0.001). Further, no patients with a DecisionDx-Melanoma-predicted risk of SLN positivity of less than 5% who decided to have an SLNB had a positive SLN (0/58 patients). Further, 9.8% of patients with a DecisionDx-Melanoma-predicted risk of SLN positivity of 5% or more who had the procedure did have a positive SLN."

Additionally, the samples containing Mn ion exhibited high reactive oxygen species (ROS) generation. In conclusion, the fabricated NFs scaffolds hold promising potential for cancer therapy.

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.

P=N/A, N=30, Recruiting, Mayo Clinic

"First Abstract: Addressing Immunotherapy Resistance in NSCLC - In collaboration with Dr. Arutha Kulasinghe of The University of Queensland and Dr. David Rimm from Yale University, the first abstract profiles the metabolic states of tumor and immune cells in NSCLC patients treated with checkpoint inhibitors....Second Abstract: Integrating Spatial Biomarker Analysis in Melanoma - The second abstract, in collaboration with Dr. Paolo Ascertio and Lunaphore, a Bio-Techne brand, examines the spatial proteomic profile of melanoma patients undergoing immunotherapy as part of the SECOMBIT trial."

These findings further substantiate the hypothesis that SAMS and epithelioid FH may represent a morphologic and genetic spectrum. The differential diagnosis, clinical follow up, and the molecular genetic findings will be discussed.

This study shows the clinical range of cutaneous lesions of BPDCN. Despite the absence of a gold standard therapy, patients treated with myeloablative intensive regimens and allo-HSCT seem to have a more favorable prognosis.

Analysis of a previously identified type-I IFN resistance gene set indicates that only a proportion of these genes was exclusive for the IFN-treated metastases reflecting a possible selective genomic pressure of endogenous IFNs during progression. Our data suggest that previous type-I IFN treatment and/or endogenous IFN production by immune response affect genomic progression of melanoma which may have clinical relevance, potentially influence immune checkpoint regulation in the tumor microenvironment.

DTL gene may be a prognosis marker and represent a unique potential target for melanoma patients. DTL supports the biologically malignant activity of melanoma cells via the ERK/E2F1/BUB1 axis.

In concordance with studies of background risk, AEs were more common in patients with CV risk enrichment, particularly those aged ≥ 65 years. Tofacitinib effectiveness/persistence were generally similar regardless of CV risk enrichment. These findings support individualised treatment benefit-risk assessment, including CV assessment/management, to optimise RA outcomes.

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