Melanoma

P2, N=90, Recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial completion date: Mar 2027 --> Jul 2027 | Trial primary completion date: Mar 2027 --> Jul 2027

P1/2, N=5, Active, not recruiting, Case Comprehensive Cancer Center | Recruiting --> Active, not recruiting | N=15 --> 5

P1, N=200, Recruiting, BeiGene | Active, not recruiting --> Recruiting | N=37 --> 200 | Trial completion date: May 2026 --> Dec 2026 | Trial primary completion date: May 2025 --> Dec 2026

The inhibitory processes downregulate GPX4, increase apoptotic proteins like Bax, and promote mixed cell death involving both ferroptosis and apoptosis. Overall, this study offers new insights and strategies for the development of GSH-responsive theranostic agents, highlighting their potential for application in tumor diagnosis and therapy.

PLEK2 is upregulated in UVM and correlates with poor patient prognosis, likely influencing the calcium signaling pathway. PLEK2 represents a promising prognostic biomarker and therapeutic target for UVM.

Our findings highlight the critical role of RT-related genes in predicting SKCM prognosis and guiding personalized therapy strategies, particularly in the context of immunotherapy. These contribute to understanding the role of radiotherapy combined with immunotherapy in melanoma.

Overall, our work provides new insights into the immunological landscape sustaining favorable clinical responses or resistance to first-line anti-PD1 therapy in melanoma patients. Such exploration participates in uncovering the mechanism of action of anti-PD1, discovering innovative predictive signatures of response, and paves the way to design pertinent combination strategies to improve patient clinical benefits in the future.

Our results confirm the heterogeneity of CAF in both bladder and prostate tumors and indicate that FAP is one of CAF subpopulation marker.

These apoptotic effects were closely linked to mitochondrial dysfunction, as evidenced by a marked loss of mitochondrial membrane potential and reduced Rh123 fluorescence in treated cells, thereby activating the intrinsic apoptotic pathway. These findings highlight the critical role of mitochondrial disruption in the cytotoxic mechanisms of these ent-kaurenes and underscore their potential as promising anticancer agents.

These effects may be attributed to the suppression of gene expression related to melanogenesis, including the regulator gene MITF and pigmentary genes TYR, TRP-1, and DCT, indicating effects comparable to those of the standard treatment groups with arbutin and kojic acid. Our findings indicated the potential of Hom Thong peel extracts as anti-melanogenic agents.

High baseline sCD14 level and its increase during the therapy prognosticated worse survival outcomes. Taken together, this preliminary study indicates the potential of circulating cfmDNA signatures and plasma sCD14 levels as biomarkers of clinical outcomes of ICIs.

Furthermore, it decreased microphthalmia-associated transcription factors and induced the suppression of cyclin-dependent kinase 2, hepatocyte growth factor receptor, B-cell/CLL lymphoma 2, and Ras-related proteins. Our findings suggest that the MC extract suppresses tumor survival genes by regulating PAX3, thereby ameliorating melanoma proliferation and invasion.

After 96 h from inhibitor removal, the G361 line presented signs of senescence (increased level of SA-β-galactosidase, IL-8, P-P53, G2/M and S phases of cell cycle, decreased lamin B1 and cleaved lamin B1), while the A375 line demonstrated more signs of apoptosis (increased subG1 phase, P-P53, cleaved lamin B1). The gathered findings suggest that MZB resulted in the induction of cellular senescence (line G361) or enhanced apoptosis (line A375) in the melanoma cell lines tested here and could be a promising therapeutic factor in malignant melanoma treatment.

Molecular docking identified potential protein targets, related to the CEO anticancer activity, in the form of PI3Kα, where the highest active theoretical inhibitor was calamenene (-7.5 kcal/mol). Docking results also showed that calamenene was the overall most active theoretical inhibitor for all docked proteins and indicated a potential presence of synergistic effects among all CEO constituents.

Background/Objective: Dabrafenib and trametinib (D + T) have been approved for the treatment of stage III melanoma with BRAF V600E V600K mutations in an adjuvant setting, based on the results from the COMBI-AD trial. Similarly, the median OS was not reached, with OS rates of 96.4% at 12 months and 92.5% at 24 months. D + T achieved an RFS benefit, with effects sustained beyond the treatment period, indicating positive outcomes in this patient population.

Our findings unveil the potential of laminB1 as both a diagnosis marker and a therapeutic target of melanoma.

After the advent of systemic therapies, a trial of the combination targeted therapy of dabrafenib plus trametinib toward BRAF V600-mutant nodal cutaneous melanoma showed that all 35 patients achieved a pathological response...For those tumours that do recur in-field, there are now competing therapies like Talimogene laherparepvec or T-VEC. Generally, ART is now used at the first recurrence. The challenge now is to find which melanomas are truly radiosensitive if ART is to have any future role in this scenario.

Our results confirm cancer-kidney crosstalk in specific cancer types. In the era of precision medicine, further research is essential to identify at-risk oncology populations, enabling early detection and management of renal complications.

CHEMBL82047 and CHEMBL381163 are ideal compounds for inhibiting MMP9. The findings of this study will contribute to the design and improvement of MMP9-targeting drugs.

Toxicities associated with systemic administration of 21h10 could be mitigated by TNFα blockade without compromising antitumor efficacy. In the tumor microenvironment, 21h10 induced highly cytotoxic antitumor T cells from clonotypes with a range of affinities for endogenous tumor antigens, robustly expanding low-affinity cytotoxic T cells and driving high expression of interferon-

We show that pirin-binding compounds can raise cellular quercetin levels. Further studies will be required to fully understand pirin's biological mechanisms.

IFNγ inhibits oxidative phosphorylation, which is required for proliferation and acquisition of the pathologic transcriptional state. Our data indicate that IFNγ induces a phenotypic switch in tumor-associated lymphatic vessels to reinforce canonical immune surveillance and block metastasis.

Furthermore, decreased tumor volume is correlated with a decreased DNA damage signature and increased apoptotic markers, indicating a role for αSyn in modulating the DNA damage response (DDR) pathway. Overall, our study provides evidence that targeting αSyn and its role in modulating the DDR and melanomagenesis could serve as a promising new therapeutic target.

Furthermore, we find that specific spatial features such as co-clustering of activated CD8+ T cells and macrophages in the pretreatment samples determine the fate of the tumor progression, despite stochastic fluctuations and changes over the treatment course. Our framework enables the determination of mechanisms of interplay between a key subset of tumor and immune cells in the TME that regulate clinical response to ICIs.

Furthermore, MHC-I downregulation and decreased infiltration with CD8+ T-cells is also associated with resistance to ICI. Our results suggest that analyses of MHC-I expression and CD8+ T-cell infiltration patterns could serve as future biomarkers to guide the decision to treat patients in early stages of melanoma with ICI.

P1/2, N=607, Completed, Bristol-Myers Squibb | Active, not recruiting --> Completed | N=425 --> 607

P1/2, N=12, Completed, Ultimovacs ASA | Active, not recruiting --> Completed

P=N/A, N=13, Active, not recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial completion date: Dec 2025 --> Sep 2025

P2, N=40, Recruiting, ImmunityBio, Inc. | Active, not recruiting --> Recruiting | N=147 --> 40

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

P1, N=40, Recruiting, Microbiotica Ltd | Not yet recruiting --> Recruiting

Real-world data suggest that adjuvant TT may be associated with better RFS and DMFS in stage III BRAF V600-mutated melanoma compared to ICI.

The P-selectin-targeted nanoparticles showed enhanced accumulation in 3D spheroids and tissues of P-selectin-expressing BRAF-mutated melanomas and BRCA-mutated breast cancers, resulting in superior in vivo efficacy and safety. This nanoplatform could advance the codelivery of a plethora of anticancer drug combinations to various P-selectin-expressing tumors.

Although the bispecific tebentafusp is FDA-approved, immunotherapy has largely failed, likely given the poorly immunogenic nature of UM...In particular, the CPT1 inhibitor, etomoxir, induced propidium iodide uptake, caspase 3 cleavage and the release of HMGB1 and IL-1β, indicating that the observed cleavage of gasdermins led to pyroptosis...Together, these data show that metabolic inhibitors can induce pyroptosis in UM cell lines, potentially offering an approach to enhance inflammation-mediated immune targeting in metastatic UM patients. Implications: Induction of pyroptosis by metabolic inhibition may alter the tumor immune microenvironment and improve the efficacy of immunotherapy in uveal melanoma.

Increased neutrophil-lymphocyte ratio (NLR) and CRP were independent risk factors for PJP occurrence, while trimethoprim-sulfamethoxazole (TMP/SMZ) prophylaxis was an independent protective factor (all p<0.05)...Mortality in PJP+ patients is primarily concentrated within the first 3 months, associated with RPILD. Early intervention with corticosteroids and prophylactic measures are crucial in reducing mortality.

The responses required RAG2 but not interferons, and cured mice developed immunity to cancer rechallenge requiring CD8+ T cells. These studies provide a framework for enhancing microbial and small molecule innate agonists for cancer, via co-activating STING and TLRs.

P1, N=196, Recruiting, Nanjing Immunophage Biotech Co., Ltd | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Sep 2025

TGF-β pathway activation showed no significant relation with treatment response to ICI or survival in patients with advanced melanoma. Hedgehog PAS was identified as a possible biomarker associated with both treatment response and survival.

Sunitinib for c-KIT mutations did not meet the primary end point, but in this small sample size, a potential signal cannot be ruled out. Rate of eligible c-KIT mutations was low, affecting accrual to this arm.

This is the first time that lentiviral structural protein has been found to have antagonistic effects on MAVS pathway. Overall, our study reveals a novel mechanism by which equine lentiviruses can evade host innate immunity, and provides insight into potential therapeutic strategies for the control of lentivirus infection.

We report a case of successful management of anti-MDA5-positive JDM complicated by RP-ILD using a combination of immunosuppressive agents, plasma exchange, and tocilizumab. Tocilizumab may serve as an effective adjunctive treatment option for patients with refractory anti-MDA5-positive JDM complicated by RP-ILD who do not respond to conventional intensive immunosuppressive therapies.

P1/2, N=58, Recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2024 --> Nov 2025 | Trial primary completion date: Dec 2024 --> Nov 2025