Malignant Melanoma: An Overview, New Perspectives, and Vitamin D Signaling

Cancers, Journal Year: 2024, Volume and Issue: 16(12), P. 2262 - 2262

Published: June 18, 2024

Melanoma, originating through malignant transformation of melanin-producing melanocytes, is a formidable malignancy, characterized by local invasiveness, recurrence, early metastasis, resistance to therapy, and high mortality rate. This review discusses etiologic risk factors for melanoma, diagnostic prognostic tools, including recent advances in molecular biology, omics, bioinformatics, provides an overview its therapy. Since the incidence melanoma rising remains unacceptably high, we discuss inherent properties, melanogenesis, that make this disease resilient treatment propose use AI solve above complex multidimensional problems. We provide on vitamin D anticancerogenic report field can solutions prevention and/or therapy melanoma. Experimental papers clinicopathological studies role status signaling pathways initiated active metabolites prognosis are reviewed. conclude signaling, defined specific nuclear receptors selective activation hydroxyderivatives, benefit new or existing therapeutic approaches. target with computational biology tools solution problem.

Language: Английский

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The role of mitophagy-related genes in prognosis and immunotherapy of cutaneous melanoma: a comprehensive analysis based on single-cell RNA sequencing and machine learning

Immunologic Research, Journal Year: 2025, Volume and Issue: 73(1)

Published: Jan. 11, 2025

Language: Английский

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Angiogenesis Still Plays a Crucial Role in Human Melanoma Progression

Cancers, Journal Year: 2024, Volume and Issue: 16(10), P. 1794 - 1794

Published: May 8, 2024

Angiogenesis plays a pivotal role in tumor progression, particularly melanoma, the deadliest form of skin cancer. This review synthesizes current knowledge on intricate interplay between angiogenesis and microenvironment (TME) melanoma progression. Pro-angiogenic factors, including VEGF, PlGF, FGF-2, IL-8, Ang, TGF-β, PDGF, integrins, MMPs, PAF, modulate contribute to metastasis. Additionally, cells within TME, such as cancer-associated fibroblasts, mast cells, melanoma-associated macrophages, influence Anti-angiogenic therapies, while showing promise, face challenges drug resistance tumor-induced activation alternative angiogenic pathways. Rational combinations anti-angiogenic agents immunotherapies are being explored overcome resistance. Biomarker identification for treatment response remains crucial personalized therapies. highlights complexity underscores need innovative therapeutic approaches tailored dynamic TME.

Language: Английский

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The Dynamic Landscape of the Coagulome of Metastatic Malignant Melanoma

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(4), P. 1435 - 1435

Published: Feb. 8, 2025

The local expression of coagulation-related genes defines the tumor coagulome. coagulome plays a pivotal role in cancer-associated thrombosis (CAT) and hemostatic complications, such as venous thromboembolism (VTE), which are frequent patients with advanced/metastatic cancer. Genomic analyses human tumors, skin cutaneous melanoma (SKCM), have unveiled complexity metastatic trajectories. However, no study to date has focused on along these Using bulk-tumor single-cell primary SKCM, metastastic samples circulating cells (CTCs), we explored SKCM progression. We identified consistent changes metastases compared tumors observed site specificity. Compared other sites, lung had specific higher F3, encoding Tissue Factor. Single-cell were used chart inter- intra-tumor heterogeneity characterize SKCM. found that subpopulation CTCs from expressed high levels platelet genes, suggesting contribution CTC–platelet interactions CTC These findings highlight dynamic properties its link cancer

Language: Английский

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Discovery of Active Ingredients Oleanolic Acid, Ursolic Acid, and Arbutin for in Vitro Anti-Melanoma: Network Pharmacology and Experimental Validation

Natural Product Communications, Journal Year: 2025, Volume and Issue: 20(1)

Published: Jan. 1, 2025

Objective Antitumor effects of the medicinal herb Prinsepia utilis Royle ( P. utilis) have been reported. This study aimed to identify potential functional components and molecular mechanisms in treatment melanoma through network pharmacology experimental verification. Methods Bioinformatics database analysis platform Chinese medicine system were used obtain active utilis, targets predicted by Swiss Target Prediction database. Disease associated with retrieved from Genecard Network topology enrichment conducted screen out core related signal pathways. The docking method was employed evaluate target binding bioactive ingredients a biology approach performed predict verify mechanism treating melanoma. Results KEGG pathway revealed multiple cancer-related pathways signaling Oleanolic acid (OA), Ursolic (UA), Arbutin are utilis. crude extract able inhibit melanin A375 cells. compounds OA UA can significantly growth migration ability human cells while inducing apoptosis inhibiting tyrosinase activity synthesis. In contrast, arbutin does not show obvious performance these biological activities. Conclusion These findings suggest that promising as more effective anti-melanoma conclusion, studies protect against regulating tyrosine melanogenesis.

Language: Английский

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Unveiling ac4C modification pattern: a prospective target for improving the response to immunotherapeutic strategies in melanoma

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: March 6, 2025

Emerging evidence has confirmed the inextricable connection between N4-acetylcytidine (ac4C) mRNA modification and clinical characteristics of malignancies. Nonetheless, it is uncertain whether how ac4C patterns affect outcomes in melanoma patients. This research integrated single-cell sequencing data transcriptomics to pinpoint ac4C-related genes (acRG) linked progression evaluate their implications. Cells with elevated acRG score were predominantly located within melanocytes cluster. Intercellular communications other cell subtypes markedly strengthened acRG-high group. We developed an excellent acRG-related signature (acRGS) utilizing a comprehensive set 101 algorithm combinations derived from 10 machine learning algorithms. Hereby, acRGS, including MYO10, ZNF667, MRAS, SCO2, MAPK10, PNMA6A, KPNA2, NT5DC2, BAIAP2L2 NDST3, delineated ac4C-associated melanoma. The acRGS possesses distinctly superior performance 120 previously reported signatures could predict overall survival patients across four external datasets. substantial associations among immune checkpoint genes, infiltration, tumor mutation burden indicate that helpful identifying who are sensitive immunotherapy. Besides, we MYO10 was mainly overexpressed tissues, positively correlated malignant phenotypes unfavorable prognosis Silencing expression inhibited proliferation, migration invasion vitro as well growth vivo. Taken together, function reliable prospective tool improve for individuals.

Language: Английский

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Cancer stem-like cells in uveal melanoma: novel insights and therapeutic implications

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2024, Volume and Issue: 1879(3), P. 189104 - 189104

Published: May 1, 2024

Uveal melanoma (UM) is the most common primary ocular tumor in adult population. Even though these tumors are successfully treated 90% of cases, almost 50% patients ultimately develop metastasis, mainly liver, via hematological dissemination, with a median survival spanning from 6 to 12 months after diagnosis. In this context, chemotherapy regimens and molecular targeted therapies have demonstrated poor response rates failed improve survival. Among multiple reasons for therapy failure, presence cancer stem-like cells (CSCs) represents main cause resistance anticancer therapies. last few years, existence CSCs UM has been both preclinical clinical studies, new pathways mechanisms described subpopulation cells. Here, we will discuss state art CSC biology their potential exploitation as therapeutic target UM.

Language: Английский

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Unraveling the landscape of non-melanoma skin cancer through single-cell RNA sequencing technology

Frontiers in Oncology, Journal Year: 2024, Volume and Issue: 14

Published: Nov. 4, 2024

Non-melanoma skin cancer (NMSC) mainly includes basal cell carcinoma, cutaneous squamous and Merkel showing a low mortality rate but the highest incidence worldwide. In recent decades, research has focused on understanding pathogenesis clinical treatments of NMSC, leading to significant advances in our knowledge these diseases development novel therapies, including immunotherapy. Nevertheless, moderate objective response rate, high recurrence, therapeutic resistance remain persistent challenges, which are partly attributable intratumoral heterogeneity. This heterogeneity indicates that tumor cells, immune stromal cells microenvironment can be reshaped series phenotypic transcriptional states vary invasiveness treatment responsiveness. The advent single-cell RNA sequencing (scRNA-seq) enabled comprehensive profiling gene expression at level, been applied NMSC quantify compositions, define states, understand evolution, discern drug resistance. this review, we highlight key findings, with focus mechanism as revealed by scRNA-seq. Furthermore, propose potential avenues for future using

Language: Английский

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Single-Nuclei Transcriptome Profiling Reveals Intra-Tumoral Heterogeneity and Characterizes Tumor Microenvironment Architecture in a Murine Melanoma Model

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(20), P. 11228 - 11228

Published: Oct. 18, 2024

Malignant melanoma is an aggressive cancer, with a high risk of metastasis and mortality rates, characterized by cancer cell heterogeneity complex tumor microenvironment (TME). Single biology ideal powerful tool to address these features at molecular level. However, this approach requires enzymatic dissociation that can influence cellular coverage. By contrast, single nucleus RNA sequencing (snRNA-seq) has substantial advantages including compatibility frozen samples the elimination dissociation-induced, transcriptional stress response. To better profile understand functional diversity different components in progression, we performed snRNA-seq 16,839 nuclei obtained from along growth murine syngeneic model carrying BRAFV600E mutation collected 9 days or 23 after subcutaneous injection. We defined 11 subtypes clusters among malignant cells 5 subsets myeloid display distinct global program enrichment early advanced stage growth, confirming was useful accurately identify intratumor dynamics during evolution. The current study offers deep insight into highlighting TME reprogramming through initiation underlying further discovery new biomarkers which may be potentially druggable.

Language: Английский

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Special Issue “Drug Discovery and Application of New Technologies”

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(21), P. 11756 - 11756

Published: Nov. 1, 2024

Historically, drug discovery and development have proven to be time-consuming costly, with the process averaging around 15 years costing approximately USD 2 billion bring a new small-molecule market [...].

Language: Английский

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