Melanoma Research最新文献

{"title":"Comprehensive analysis and external validation of a glycolysis-related gene signature as a prognostic index for skin cutaneous melanoma.","authors":"Chenshan Jiang, Sen Niu, Chen Li, Anna Liu, Mingjian Zhao, Weihao Wang, Wei Shen, Xiaojun Tang","doi":"10.1097/CMR.0000000000001143","DOIUrl":"https://doi.org/10.1097/CMR.0000000000001143","url":null,"abstract":"<p><p>Skin cutaneous melanoma (SKCM) is the third most common cause of cancer-related deaths globally. Today, precise biomarkers to predict melanoma prognosis are quite limited. Aerobic glycolysis serves as the primary metabolic pathway for malignancies to meet their rapid growth demands. This study built a glycolysis-associated gene (GAG) signature to evaluate prognosis and immunotherapy response of SKCM. Data acquired from the Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) databases were evaluated to obtain differentially expressed GAGs. With machine learning techniques, four key GAGs (GOT2, CLN6, GYS1, and IDUA) were pinpointed as candidate prognostic biomarkers. Subsequently, a risk model was constructed by incorporating these four GAGs. The risk model could effectively forecast SKCM patient survival and treatment efficacy. Also, the elevated risk scores correlated with diminished immune cell infiltration and impaired immune functions. In addition, the four GAGs all showed influence on immune cell infiltrations of SKCM. Then, the role of predominant hub gene GYS1 and CLN6 was validated using in vitro models. The overexpression of GYS1 and CLN6 could promote viability, invasion, and proliferation of melanoma cells. ELISA and western blot experiments demonstrated that the overexpression of GYS1 lead to higher secretion of proinflammatory cytokine TNF-α and IL-1β, activated the nuclear factor kappa B signaling pathway, and promoted an immunosuppressive microenvironment. Collectively, this study initially pinpointed glycolysis-related genes as prognostic biomarkers for melanoma and elucidated the facilitating role of GYS1 and CLN6 in melanoma, providing deeper insights into pathogenesis of melanoma.</p>","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149111942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive role of fluorine-18-labeled fluorodeoxyglucose PET/computed tomography across the disease course of primary malignant melanoma of the esophagus.","authors":"Fei Wang, Xiangxi Meng, Rui Guo, Xin Zhou, Hua Su, Yang Liu, Zhi Yang, Nan Li","doi":"10.1097/CMR.0000000000001142","DOIUrl":"https://doi.org/10.1097/CMR.0000000000001142","url":null,"abstract":"<p><p>This study aimed to evaluate the clinical value of fluorine-18-labeled fluorodeoxyglucose (18F-FDG) PET/computed tomography (CT) in managing primary malignant melanoma of the esophagus (PMME). Seventy patients with pathologically confirmed PMME between September 2011 and June 2025 were retrospectively analyzed. The diagnostic performance of 18F-FDG PET/CT was analyzed for evaluating primary tumors, lymph nodes, recurrence, metastasis, and its role in predicting treatment response. Among 20 patients who underwent preoperative evaluation, no significant differences in 18F-FDG uptake or tumor wall thickness were observed between T1 and T2/T3 tumors (all P > 0.05). Lesion-based analysis revealed that the area under the receiver operating characteristic curve for lymph node evaluation was 0.923 for 18F-FDG PET/CT and 0.738 for contrast-enhanced CT, with sensitivities of 82.6 and 47.8%, and specificities of 98.0 and 97.0%, respectively. Among 25 patients who received nonsurgical treatment, significant differences were found in maximum standardized uptake value, metabolic tumor volume (MTV), total lesion glycolysis (TLG), and tumor wall thickness between responders and nonresponders (all P < 0.05). Multivariate analysis identified TLG as an independent predictor of treatment response (odds ratio = 0.950, P = 0.025). In 50 patients evaluated for distant metastases and postoperative recurrence, additional findings from 18F-FDG PET/CT led to significant management changes in 14.0% of patients (7/50). 18F-FDG PET/CT is highly effective for evaluating lymph nodes and distant metastases in PMME, and facilitates early identification of patients likely to respond to treatment. It may serve as a valuable tool for staging, response prediction, and follow-up of patients with PMME.</p>","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149111920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of circulating tumor DNA in the management of melanoma: a literature review.","authors":"Victoria Dos Santos, John Ochieng, Sahar Borna, Rajendra Sawh-Martinez","doi":"10.1097/CMR.0000000000001117","DOIUrl":"10.1097/CMR.0000000000001117","url":null,"abstract":"<p><p>Circulating tumor DNA (ctDNA) is an emerging noninvasive biomarker in melanoma, yet its clinical relevance varies by disease stage and tumor biology. This literature review integrates mechanistic concepts with clinical evidence to clarify where ctDNA provides meaningful insight for melanoma management. A comprehensive review of recent literature was conducted to evaluate biological mechanisms, detection methods, and clinical applications of ctDNA in melanoma care. Across multiple studies, detectable baseline ctDNA was consistently associated with worse overall and PFS, with hazard ratios generally ranging from 2 to 3. Low or undetectable pretreatment ctDNA correlated with improved outcomes in patients receiving immune checkpoint inhibitors and targeted therapies. Early ctDNA decline or clearance during treatment was associated with radiographic response, whereas persistent detectability suggested intrinsic resistance. Serial monitoring enabled identification of emerging resistance mutations, including NRAS, MEK1, and PI3K-pathway alterations, frequently preceding radiographic progression. In resected stage III melanoma, postoperative ctDNA positivity strongly predicted relapse, with hazard ratios approaching 10, and molecular recurrence often preceded clinical recurrence by several months. By contrast, early-stage melanoma demonstrated low ctDNA detection rates, often below 15%, reflecting limited tumor burden and low DNA shedding. Evidence is emerging to position ctDNA as a dynamic biomarker that complements conventional melanoma staging by capturing real-time tumor burden, treatment response, and residual disease. Its clinical utility is most robust in high-risk and advanced melanoma, where ctDNA reliably informs prognosis, molecular residual disease, and early relapse, while sensitivity constraints limit its current role in early-stage disease with low tumor burden.</p>","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":" ","pages":"353-361"},"PeriodicalIF":1.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148302299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dissecting cellular heterogeneity across two ocular melanoma subtypes by single-cell RNA sequencing.","authors":"Ziqi Gong, Fenghao Zhang, Yuxian Feng, Lirong Wu, Jing Tu","doi":"10.1097/CMR.0000000000001119","DOIUrl":"10.1097/CMR.0000000000001119","url":null,"abstract":"<p><p>Ocular melanoma, the most common primary ocular malignancy in adults, is a rare subtype of melanoma characterized by high malignancy and poor prognosis. The aim of this study is to investigate the tumor cells and microenvironmental heterogeneity in two ocular melanoma subtypes at the single-cell level. We performed single-cell analysis across 28 ocular melanoma samples, including 14 uveal melanoma and 14 conjunctival melanoma (CoM) samples. Tumor cells and immune cells were analyzed to investigate the heterogeneous cellular composition in the tumor microenvironment. We compared the transcriptome profile of uveal melanoma and CoM to uncover subtype-specific biological signatures and molecular programs. Compared with uveal melanoma, CoM exhibited significantly higher immune cell infiltration. Tumor cells from the two subtypes displayed distinct transcriptional states and functional pathway activities. CoM was enriched for melanoma subpopulations characterized by epithelial-mesenchymal transition-related and stemness-associated transcriptional programs, together with relatively higher copy number variation scores, suggesting transcriptional and genomic features previously associated with more aggressive tumor behavior. While uveal melanoma was characterized by CD8 + T cells with relatively higher cytotoxicity- and terminal exhaustion-associated activities, CoM exhibited comparatively lower cytotoxicity and terminal exhaustion signatures but higher progenitor-like and exhausted-like effector features. CoM also showed increased infiltration of monocytes and CXCL3+ tumor-associated macrophages with elevated M2-associated signature activity. Our study provides a comprehensive comparison between two ocular melanoma subtypes at the single-cell level, revealing distinct cellular compositions, transcriptional state distributions, and molecular programs of tumor cells, as well as immune microenvironmental features.</p>","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":" ","pages":"391-406"},"PeriodicalIF":1.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148397142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A modern review of uveal melanoma: molecular insights, clinical management, and emerging therapies.","authors":"Bhanupriya Dhabhai, Abhijit Beura, Janvi Bhatankar, Arisha Imam, Narendra Kumar Sharma, Anita Rana, Amit Sharma, Pawan Kumar Maurya, Ingo Gh Schmidt-Wolf, Abhishek Kumar, Tikam Chand Dakal","doi":"10.1097/CMR.0000000000001124","DOIUrl":"10.1097/CMR.0000000000001124","url":null,"abstract":"<p><p>Uveal melanoma is the most frequent primary intraocular malignancy in adults and is characterized by an aggressive clinical course, high propensity for hepatic metastasis, and poor survival after metastatic progression. Improvements in ocular imaging and local therapies have improved primary tumor control, but approximately half of patients will ultimately develop metastatic disease with poor treatment options. Recent advances in genomics and molecular biology have dramatically improved our understanding of uveal melanoma pathogenesis, with the discovery of activating mutations in GNAQ , GNA11 , CYSLTR2 , and PLCB4 as early oncogenic events that drive aberrant signaling through the protein kinase C (PKC), MAPK, PI3K/AKT, and Hippo-YAP pathways. Additional changes in BAP1 , SF3B1 , and EIF1AX as well as common chromosomal aberrations, contribute to tumor progression, metastatic risk and clinical heterogeneity. New insights into the distinct immune landscape of uveal melanoma, including low tumor mutational burden, immune-desert and immune-excluded phenotypes, a macrophage-dominant microenvironment, and hepatic immune tolerance, have provided important explanations for its poor response to conventional immunotherapies. This review summarizes current knowledge on the epidemiology, risk factors, molecular pathogenesis, tumor microenvironment, diagnostic innovations and prognostic biomarkers of UM. We also review novel developments in molecular profiling, liquid biopsy, artificial intelligence-assisted diagnostics, and precision oncology strategies, as well as novel therapeutic approaches such as tebentafusp, protein kinase C inhibitors, immune checkpoint inhibitors, adoptive cell therapies, and liver-directed therapies. These advances are together changing the clinical management of uveal melanoma and provide new opportunities for personalized treatment, earlier detection of metastatic disease and improved patient outcomes.</p>","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":" ","pages":"362-380"},"PeriodicalIF":1.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148456459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of chemokine and chemokine receptor gene variants with occurrence of multiple primary melanoma.","authors":"Irene Orlow, Li Luo, Isidora Autuori, Isam Mina, Audrey Mauguen, Sharon N Edmiston, Richard P Gallagher, David W Ollila, Tim Lee, Klaus Busam, Anne E Cust, Marianne Berwick, Colin B Begg, Peter A Kanetsky, Nancy E Thomas","doi":"10.1097/CMR.0000000000001128","DOIUrl":"10.1097/CMR.0000000000001128","url":null,"abstract":"<p><p>Chemokine and chemokine receptors (CKRs) regulate cell growth, tumor immunity, migration, angiogenesis, and metastasis. We evaluated associations of inherited chemokine/CKR variants with subsequent primary melanomas among patients with a previous melanoma. Our population-based cohort included 2458 incident single primary and 1205 multiple primary melanoma (MPM) cases. We examined 215 a priori candidate polymorphisms selected based on prior evidence and predicted functional relevance, along with nine haplotype blocks. Logistic regression estimated odds ratios and 95% confidence intervals, adjusting for age at diagnosis, sex, age-by-sex interaction, and study center. Thirty variants across 14 genes were nominally associated with MPM ( P  < 0.05), with effect sizes ranging from 16 to 80%. Five haplotypes in CXCL12 , CCL18 , CXCR2 , and CCR9 were significantly associated with MPM ( Pglobal < 0.03) with stronger effects than individual-effect alleles. Functional annotation identified 160 associated index variants and linkage disequilibrium proxies acting as skin expression quantitative trait loci for CXCR2 , XCR1 , BCL9L , FYCO1 , PNKD , RUFY4 , and RP11-378A13.1 ( P < 1.06E-05 to 4.3E-34). These variants were classified functionally as candidate causal variants based on convergent regulatory annotation and skin‑specific expression quantitative trait locus evidence, linking chemokine/CKR variants and haplotypes to downstream genes involved in epithelial-mesenchymal-like transition, matrix remodeling, and other tumorigenic processes, thereby implicating immune regulatory mechanisms in melanoma development. To the best of our knowledge, this is the first study to demonstrate an association of a priori chemokine/CKR variants with subsequent melanoma risk. Validation and evaluation of associations with tumor characteristics and survival are warranted.</p>","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":" ","pages":"461-471"},"PeriodicalIF":1.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13505304/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148670016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spatial T lymphocyte infiltration into the primary melanoma tumor associates with survival.","authors":"Sharon N Edmiston, Yi-Hsuan S Tsai, David L Corcoran, Honglin Hao, Eloise A Parrish, Paul B Googe, Ronglai Shen, Pei Fen Kuan, David W Ollila, Kathleen Conway, Nancy E Thomas","doi":"10.1097/CMR.0000000000001127","DOIUrl":"10.1097/CMR.0000000000001127","url":null,"abstract":"<p><p>Tumor infiltrating lymphocyte grade is a prognostic indicator for patients with cutaneous invasive primary melanoma and assigned one of three-levels (brisk, nonbrisk, or absent). We sought to develop objective, quantitative measures of T lymphocyte subtypes spatially within the tumor microenvironment. We applied multiplex whole-slide immunohistochemistry/immunofluorescence to 80 melanomas, using S100 to identify tumor cells (S100+) and CD3 and CD8 to identify noncytotoxic T lymphocytes (CD3+CD8-), cytotoxic CD8+ T lymphocytes (CD3+CD8+), and total T lymphocytes (CD3+CD8- plus CD3+CD8+). We used image analysis to spatially locate the T lymphocyte subtypes within the whole tumor, the tumor center (175 µm into the tumor), and the tumor margin (within 100 µm outside the tumor). T lymphocyte subtypes were quantified for density as CD3+CD8- and CD3+CD8+ cells colocalized with intact nuclei/µm 2 . Melanoma-specific survival, adjusted for American Joint Committee on Cancer eighth edition stage, improved when a higher density of each T lymphocyte subtype (CD3+CD8-; CD3+CD8+) infiltrated 175 µm into the tumor center or total T lymphocytes infiltrated into the whole tumor (hazard ratios: 0.72-0.77; all P  < 0.05). Improved melanoma-specific survival is significantly associated with high density of CD3+CD8- T lymphocytes in the margin after stage adjustment. Our results indicate spatial location of T lymphocyte subset infiltration within the tumor microenvironment is important for predicting melanoma-specific survival.</p>","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":" ","pages":"424-435"},"PeriodicalIF":1.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13537756/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148604974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hemophagocytic lymphohistiocytosis and posterior reversible encephalopathy syndrome during BRAF/MEK inhibitor therapy following immune checkpoint blockade in metastatic melanoma: a case report.","authors":"Nina Bonkat, Jonas Hafele, Ivan Tancevski","doi":"10.1097/CMR.0000000000001120","DOIUrl":"10.1097/CMR.0000000000001120","url":null,"abstract":"<p><p>Hemophagocytic lymphohistiocytosis (HLH) is a rare but potentially life-threatening hyperinflammatory syndrome characterized by uncontrolled immune activation and cytokine release. Secondary HLH has increasingly been reported in association with modern oncologic therapies, including immune checkpoint inhibitors and targeted therapies for malignant melanoma. Sequential treatment with checkpoint inhibitors followed by BRAF/MEK inhibitors may further increase the risk of immune dysregulation. We report the case of a 61-year-old female with BRAF V600K-mutant metastatic melanoma (stage IV) initially treated with combination immunotherapy consisting of nivolumab and ipilimumab, followed by nivolumab monotherapy. Due to progressive disease and immune-related hypophysitis, targeted therapy with dabrafenib and trametinib was initiated. Shortly thereafter, the patient was admitted with suspected sepsis, gastroenteritis, and a trunk-predominant rash. During hospitalization, she developed hemolysis, disseminated intravascular coagulation, and acute kidney injury. Further evaluation revealed reactivation of Epstein-Barr virus, absolute lymphocytosis, and marked T-cell activation on flow cytometry. An HScore of 234 indicated a 98% probability of HLH. Under supportive treatment and immunosuppressive therapy, inflammatory markers, coagulation parameters, and renal function gradually improved. During the clinical course, the patient developed transient visual disturbances. Neuroimaging excluded cerebral ischemia, and findings were compatible with posterior reversible encephalopathy syndrome, likely secondary to HLH. Visual symptoms resolved within 2 days. This case highlights HLH as a rare but severe complication in patients receiving sequential immune checkpoint inhibition and BRAF/MEK-targeted therapy for metastatic melanoma. Early recognition of hyperinflammatory syndromes and interdisciplinary management are essential to improve clinical outcomes.</p>","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":" ","pages":"472-475"},"PeriodicalIF":1.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148579199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evidence of genetic susceptibility to immune-related dermatitis in patients with melanoma treated with immune checkpoint inhibitors.","authors":"Ahmad A Tarhini, Mohammad Ali Khaksar, Zhihua Chen, Sandra J Lee, F Stephen Hodi, Tingyi Li, Sean J Yoder, Howard Streicher, Patrick Hwu, Vernon K Sondak, John M Kirkwood, Xuefeng Wang, Peter A Kanetsky","doi":"10.1097/CMR.0000000000001118","DOIUrl":"https://doi.org/10.1097/CMR.0000000000001118","url":null,"abstract":"<p><p>Immune checkpoint inhibitor (ICI)-mediated dermatitis is a common treatment-related adverse event. We conducted single-nucleotide polymorphisms (SNPs)-array genotyping on germline DNA from 744 participants in a phase three adjuvant trial of ipilimumab in melanoma. Logistic regression was used to estimate associations between inherited genetic markers and the occurrence of dermatitis. We also tested previously reported dermatitis-related polygenic risk scores (PRS) adjusting for genetic ancestry. Dermatitis of any grade occurred in 52% (232 Gr1, 97 Gr2, and 52 Gr3). We identified two SNPs associated with dermatitis and subsequently developed a two-SNP PRS that was associated with dermatitis risk and severity. Both variants mapped to intronic regions of the insulin-like growth factor 1 receptor and A-kinase anchoring protein 12 genes, which have important roles in immune regulation and inflammatory response. Separately, 11 previously reported dermatitis-related PRSs derived from general population cohorts not exposed to immunotherapy were tested and none was associated with ICI-mediated dermatitis in our cohort. The cohort-derived PRS showed modest discrimination for dermatitis risk (AUC 0.63). The incidence of dermatitis was associated with improved outcomes; patients with grade 1-2 or any-grade dermatitis demonstrated improved relapse-free survival (RFS) (hazard ratio: 0.74; P = 0.007 and 0.77, P = 0.01, respectively). The cohort-derived PRS showed a trend toward improved RFS and overall survival. In conclusion, we generated a novel PRS associated with ICI-mediated dermatitis risk and severity that demonstrated a trend towards improved survival outcomes. Our findings support a role for inherited genetic variation in relation to ICI dermatitis and warrant further investigation.</p>","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":"36 5","pages":"407-415"},"PeriodicalIF":1.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148830057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Schisandrin C suppresses melanoma growth and metastasis through modulation of Rap1-related and phosphatidylinositol 3-kinase/protein kinase B/mechanistic target of rapamycin signaling pathways.","authors":"Wenyue Zhuang, Kexin Liu, Shuangling Wang, Meihao Zhang, Shiqi Wang, Zhengyi Li","doi":"10.1097/CMR.0000000000001116","DOIUrl":"10.1097/CMR.0000000000001116","url":null,"abstract":"<p><p>Schisandrin C (Sch C), a lignan derived from Schisandra chinensis , exhibits antitumor activity in several malignancies; however, its effects on melanoma remain unclear. This study investigated the antitumor effects of Sch C on melanoma growth and metastasis and the underlying molecular mechanisms. Network pharmacology was used to predict potential targets of Sch C. In-vitro assays using B16-F10 melanoma cells evaluated proliferation, migration, invasion, apoptosis, and epithelial-mesenchymal transition (EMT). In-vivo antitumor activity was assessed in a murine melanoma xenograft model. Protein expression of key signaling molecules was analyzed by Western blotting and immunohistochemistry. Sch C significantly inhibited melanoma cell proliferation, migration, and invasion in a dose-dependent manner and promoted apoptosis. Sch C downregulated EMT-related proteins, including matrix metalloproteinase (MMP)-2, MMP-9, and vimentin, while upregulating E-cadherin. Mechanistically, Sch C reduced the phosphorylation of phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), and mechanistic target of rapamycin (mTOR) and was associated with modulation of Rap1-related signaling pathways. In vivo , Sch C markedly reduced tumor volume and weight without obvious toxicity and increased apoptosis while decreasing proliferation in tumor tissues. Sch C exerts antimelanoma effects and is associated with inhibition of PI3K/AKT/mTOR signaling and modulation of Rap1-related pathways, suggesting its potential as a therapeutic candidate for melanoma.</p>","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":" ","pages":"381-390"},"PeriodicalIF":1.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148265447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}