Nuntouchaporn Amonchaisakda, Chuda Rujitharanawong, Papapit Tuchinda, Kanokvalai Kulthanan, Leena Chularojanamontri
{"title":"Hospitalization and mortality in Asian autoimmune bullous dermatosis patients: A 17-year retrospective study","authors":"Nuntouchaporn Amonchaisakda, Chuda Rujitharanawong, Papapit Tuchinda, Kanokvalai Kulthanan, Leena Chularojanamontri","doi":"10.1111/exd.15095","DOIUrl":"https://doi.org/10.1111/exd.15095","url":null,"abstract":"<p>Limited data exist on the factors associated with hospitalization and mortality in Asian inpatients with autoimmune bullous dermatoses (AIBDs). This study aimed to elucidate the risk factors affecting hospitalization and mortality rates in Asian patients with AIBDs. A retrospective analysis of patients with AIBDs treated at Siriraj Hospital during a 17-year period was performed using the International Classification of Diseases 10th revision codes. The characteristics of inpatients and outpatients were compared, and mortality rates and associated factors were identified. The study included 360 AIBD patients (180 inpatients, 180 outpatients). Inpatients were significantly younger than outpatients. The identified risk factors for hospitalization were malignancy (odds ratio [OR] 2.83, 95% confidence interval [CI] 1.13–8.04; <i>p</i> = 0.034), moderate to severe disease (OR 2.52, 95% CI 1.49–4.34; <i>p</i> < 0.001), systemic corticosteroid use ≥15 mg/day (OR 2.27, 95% CI 1.21–4.41; <i>p</i> = 0.013) and oral cyclophosphamide treatment (OR 9.88, 95% CI 3.82–33.7; <i>p</i> < 0.001). Kaplan–Meier analysis revealed mortality rates of 26%, 36% and 39% for inpatients with pemphigus at 1, 3 and 5 years, respectively. For inpatients with pemphigoid, the corresponding rates were 28%, 38% and 47%. Infections, particularly pneumonia, were the predominant cause of death in both conditions. This study confirmed that both Asian ethnicity and healthcare disparities may be correlated with adverse outcomes in patients with AIBDs. Pemphigus mortality rates were substantially greater in Asian patients than in Caucasian patients. Continuous monitoring of factors contributing to hospitalization and mortality is imperative to improve treatment outcomes.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140919338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tong Li, Yimei Xiong, Longjun Xian, Lidan Xiong, Li Li
{"title":"YAP prevents senescence of dermal fibroblast and inhibits melanogenesis via paracrine effect of DKK1","authors":"Tong Li, Yimei Xiong, Longjun Xian, Lidan Xiong, Li Li","doi":"10.1111/exd.15093","DOIUrl":"https://doi.org/10.1111/exd.15093","url":null,"abstract":"<p>Senile skin hyperpigmentation displays remarkable histopathological features of dermal aging. The crosstalk between melanocytes and dermal fibroblasts plays crucial roles in aging-related pigmentation. While senescent fibroblasts can upregulate pro-melanogenic factors, the role of anti-melanogenic factors, such as dickkopf1 (DKK1), and the upstream regulatory mechanism during aging remain obscure. This study investigated the roles of yes-associated protein (YAP) and DKK1 in the regulation of dermal fibroblast senescence and melanogenesis. Our findings demonstrated decreased YAP activity and DKK1 levels in intrinsic and extrinsic senescent fibroblasts. YAP depletion induced fibroblast senescence and downregulated the expression and secretion of DKK1, whereas YAP overexpression partially reversed the effect. The transcriptional regulation of DKK1 by YAP was supported by dual-luciferase reporter and chromatin immunoprecipitation assays. Moreover, YAP depletion in fibroblasts upregulated Wnt/β-catenin in melanocytes and stimulated melanogenesis, which was partially rescued by the re-supplementation of DKK1. Conversely, overexpression of YAP in senescent fibroblasts decreased Wnt/β-catenin levels in melanocytes and inhibited melanogenesis. Additionally, reduced levels of YAP and DKK1 were verified in the dermis of solar lentigines. These findings suggest that, during skin aging, epidermal pigmentation may be influenced by YAP in the dermal microenvironment via the paracrine effect of DKK1.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140919339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Therapeutic modulation of KIT ligand in melanocytic disorders with implications for mast cell diseases","authors":"Alec Sevilla, James Grichnik","doi":"10.1111/exd.15091","DOIUrl":"https://doi.org/10.1111/exd.15091","url":null,"abstract":"<p>KIT ligand and its associated receptor KIT serve as a master regulatory system for both melanocytes and mast cells controlling survival, migration, proliferation and activation. Blockade of this pathway results in cell depletion, while overactivation leads to mastocytosis or melanoma. Expression defects are associated with pigmentary and mast cell disorders. KIT ligand regulation is complex but efficient targeting of this system would be of significant benefit to those suffering from melanocytic or mast cell disorders. Herein, we review the known associations of this pathway with cutaneous diseases and the regulators of this system both in skin and in the more well-studied germ cell system. Exogenous agents modulating this pathway will also be presented. Ultimately, we will review potential therapeutic opportunities to help our patients with melanocytic and mast cell disease processes potentially including vitiligo, hair greying, melasma, urticaria, mastocytosis and melanoma.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.15091","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140844782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kimberly A. Arnold, Mary C. Moran, Huishan Shi, Ivonne M. J. J. van Vlijmen-Willems, Diana Rodijk-Olthuis, Jos P. H. Smits, Matthew G. Brewer
{"title":"CLDN1 knock out keratinocytes as a model to investigate multiple skin disorders","authors":"Kimberly A. Arnold, Mary C. Moran, Huishan Shi, Ivonne M. J. J. van Vlijmen-Willems, Diana Rodijk-Olthuis, Jos P. H. Smits, Matthew G. Brewer","doi":"10.1111/exd.15084","DOIUrl":"https://doi.org/10.1111/exd.15084","url":null,"abstract":"<p>The transmembrane protein claudin-1 is critical for formation of the epidermal barrier structure called tight junctions (TJ) and has been shown to be important in multiple disease states. These include neonatal ichthyosis and sclerosing cholangitis syndrome, atopic dermatitis and various viral infections. To develop a model to investigate the role of claudin-1 in different disease settings, we used CRISPR/Cas9 to generate human immortalized keratinocyte (KC) lines lacking claudin-1 (CLDN1 KO). We then determined whether loss of claudin-1 expression affects epidermal barrier formation/function and KC differentiation/stratification. The absence of claudin-1 resulted in significantly reduced barrier function in both monolayer and organotypic cultures. CLDN1 KO cells demonstrated decreases in gene transcripts encoding the barrier protein filaggrin and the differentiation marker cytokeratin-10. Marked morphological differences were also observed in CLDN1 KO organotypic cultures including diminished stratification and reduced formation of the <i>stratum granulosum</i>. We also detected increased proliferative KC in the basale layer of CLDN1 KO organotypic cultures. These results further support the role of claudin-1 in epidermal barrier and suggest an additional role of this protein in appropriate stratification of the epidermis.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140844863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Benjamin Al, Stephan Traidl, Nicholas Holzscheck, Sina Freimooser, Hendrik Mießner, Hendrik Reuter, Oliver Dittrich-Breiholz, Thomas Werfel, Judith A. Seidel
{"title":"Single-cell RNA sequencing reveals 2D cytokine assay can model atopic dermatitis more accurately than immune-competent 3D setup","authors":"Benjamin Al, Stephan Traidl, Nicholas Holzscheck, Sina Freimooser, Hendrik Mießner, Hendrik Reuter, Oliver Dittrich-Breiholz, Thomas Werfel, Judith A. Seidel","doi":"10.1111/exd.15077","DOIUrl":"https://doi.org/10.1111/exd.15077","url":null,"abstract":"<p>Modelling atopic dermatitis (AD) <i>in vitro</i> is paramount to understand the disease pathophysiology and identify novel treatments. Previous studies have shown that the Th2 cytokines IL-4 and IL-13 induce AD-like features in keratinocytes <i>in vitro</i>. However, it has not been systematically researched whether the addition of Th2 cells, their supernatants or a 3D structure is superior to model AD compared to simple 2D cell culture with cytokines. For the first time, we investigated what <i>in vitro</i> option most closely resembles the disease <i>in vivo</i> based on single-cell RNA sequencing data (scRNA-seq) obtained from skin biopsies in a clinical study and published datasets of healthy and AD donors. <i>In vitro</i> models were generated with primary fibroblasts and keratinocytes, subjected to cytokine treatment or Th2 cell cocultures in 2D/3D. Gene expression changes were assessed using qPCR and Multiplex Immunoassays. Of all cytokines tested, incubation of keratinocytes and fibroblasts with IL-4 and IL-13 induced the closest <i>in vivo</i>-like AD phenotype which was observed in the scRNA-seq data. Addition of Th2 cells to fibroblasts failed to model AD due to the downregulation of ECM-associated genes such as <i>POSTN</i>. While keratinocytes cultured in 3D showed better stratification than in 2D, changes induced with AD triggers did not better resemble AD keratinocyte subtypes observed <i>in vivo</i>. Taken together, our comprehensive study shows that the simple model using IL-4 or IL-13 in 2D most accurately models AD in fibroblasts and keratinocytes <i>in vitro</i>, which may aid the discovery of novel treatment options.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.15077","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140844783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Samuel C. Williams, Sandra Garcet, Hong Hur, Shunsuke Miura, Juana Gonzalez, Kristina Navrazhina, Mika Yamamura-Murai, Kazuhiko Yamamura, Xuan Li, John Frew, Vincent A. Fischetti, Uri Sela, James G. Krueger
{"title":"Gram-negative anaerobes elicit a robust keratinocytes immune response with potential insights into HS pathogenesis","authors":"Samuel C. Williams, Sandra Garcet, Hong Hur, Shunsuke Miura, Juana Gonzalez, Kristina Navrazhina, Mika Yamamura-Murai, Kazuhiko Yamamura, Xuan Li, John Frew, Vincent A. Fischetti, Uri Sela, James G. Krueger","doi":"10.1111/exd.15087","DOIUrl":"https://doi.org/10.1111/exd.15087","url":null,"abstract":"<p>Hidradenitis Suppurativa (HS) is a chronic autoinflammatory skin disease with activated keratinocytes, tunnel formation and a complex immune infiltrate in tissue. The HS microbiome is polymicrobial with an abundance of commensal gram-positive facultative (GPs) <i>Staphylococcus</i> species and gram-negative anaerobic (GNA) bacteria like <i>Prevotella</i>, <i>Fusobacterium</i> and <i>Porphyromonas</i> with increasing predominance of GNAs with disease severity. We sought to define the keratinocyte response to bacteria commonly isolated from HS lesions to probe pathogenic relationships between HS and the microbiome. Type strains of <i>Prevotella nigrescens</i>, <i>Prevotella melaninogenica</i>, <i>Prevotella intermedia</i>, <i>Prevotella asaccharolytica</i>, <i>Fusobacterium nucleatum</i>, as well as <i>Staphylococcus aureus</i> and the normal skin commensal <i>Staphylococcus epidermidis</i> were heat-killed and co-incubated with normal human keratinocytes. RNA was collected and analysed using RNAseq and RT-qPCR. The supernatant was collected from cell culture for protein quantification. Transcriptomic profiles between HS clinical samples and stimulated keratinocytes were compared. Co-staining of patient HS frozen sections was used to localize bacteria in lesions. A mouse intradermal injection model was used to investigate early immune recruitment. TLR4 and JAK inhibitors were used to investigate mechanistic avenues of bacterial response inhibition. GNAs, especially <i>F. nucleatum</i>, stimulated vastly higher <i>CXCL8</i>, <i>IL17C</i>, <i>CCL20</i>, <i>IL6</i>, <i>TNF</i> and <i>IL36γ</i> transcription in normal skin keratinocytes than the GPs <i>S. epidermidis</i> and <i>S. aureus</i>. Using RNAseq, we found that <i>F. nucleatum</i> (and <i>Prevotella</i>) strongly induced the IL-17 pathway in keratinocytes and overlapped with transcriptome profiles of HS patient clinical samples. Bacteria were juxtaposed to activated keratinocytes in vivo, and <i>F. nucleatum</i> strongly recruited murine neutrophil and macrophage migration. Both the TLR4 and pan-JAK inhibitors reduced cytokine production. Detailed transcriptomic profiling of healthy skin keratinocytes exposed to GNAs prevalent in HS revealed a potent, extensive inflammatory response vastly stronger than GPs. GNAs stimulated HS-relevant genes, including many genes in the IL-17 response pathway, and were significantly associated with HS tissue transcriptomes. The close association of activated keratinocytes with bacteria in HS lesions and innate infiltration in murine skin cemented GNA pathogenic potential. These novel mechanistic insights could drive future targeted therapies.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.15087","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140814141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sejin Oh, Eunhye Yeo, Joonho Shim, Hyungrye Noh, Jihye Park, Kyeong-Tae Lee, Seok-Hyung Kim, Dongyoun Lee, Jong Hee Lee
{"title":"Revealing the pathogenesis of keloids based on the status: Active vs inactive","authors":"Sejin Oh, Eunhye Yeo, Joonho Shim, Hyungrye Noh, Jihye Park, Kyeong-Tae Lee, Seok-Hyung Kim, Dongyoun Lee, Jong Hee Lee","doi":"10.1111/exd.15088","DOIUrl":"https://doi.org/10.1111/exd.15088","url":null,"abstract":"<p>Recently, the pathomechanisms of keloids have been extensively researched using transcriptomic analysis, but most studies did not consider the activity of keloids. We aimed to profile the transcriptomics of keloids according to their clinical activity and location within the keloid lesion, compared with normal and mature scars. Tissue samples were collected (keloid based on its activity (active and inactive), mature scar from keloid patients and normal scar (NS) from non-keloid patients). To reduce possible bias, all keloids assessed in this study had no treatment history and their location was limited to the upper chest or back. Multiomics assessment was performed by using single-cell RNA sequencing and multiplex immunofluorescence. Increased mesenchymal fibroblasts (FBs) was the main feature in keloid patients. Noticeably, the proportion of pro-inflammatory FBs was significantly increased in active keloids compared to inactive ones. To explore the nature of proinflammatory FBs, trajectory analysis was conducted and CCN family associated with mechanical stretch exhibited higher expression in active keloids. For vascular endothelial cells (VECs), the proportion of tip and immature cells increased in keloids compared to NS, especially at the periphery of active keloids. Also, keloid VECs highly expressed genes with characteristics of mesenchymal activation compared to NS, especially those from the active keloid center. Multiomics analysis demonstrated the distinct expression profile of active keloids. Clinically, these findings may provide the future appropriate directions for development of treatment modalities of keloids. Prevention of keloids could be possible by the suppression of mesenchymal activation between FBs and VECs and modulation of proinflammatory FBs may be the key to the control of active keloids.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.15088","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140814119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cristian Fidanzi, Michela Iannone, Matteo Bevilacqua, Marco Romanelli, Giovanni Bagnoni, Gaetano De Rosa, Giuseppe Nicolò Fanelli, Cristian Scatena, Agata Janowska
{"title":"Follicular melanoma—A rare entity: First description of an association with a nevus","authors":"Cristian Fidanzi, Michela Iannone, Matteo Bevilacqua, Marco Romanelli, Giovanni Bagnoni, Gaetano De Rosa, Giuseppe Nicolò Fanelli, Cristian Scatena, Agata Janowska","doi":"10.1111/exd.15086","DOIUrl":"https://doi.org/10.1111/exd.15086","url":null,"abstract":"","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140814140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Heng Yin, Hui Chen, Wei Zhang, Jing Zhang, Tao Cui, Yunpeng Li, Nan Yu, Yingyao Yu, Hai Long, Rong Xiao, Yuwen Su, Yaping Li, Guiying Zhang, Yixin Tan, Haijing Wu, Qianjin Lu
{"title":"Image-based remote evaluation of PASI scores with psoriasis by the YOLO-v4 algorithm","authors":"Heng Yin, Hui Chen, Wei Zhang, Jing Zhang, Tao Cui, Yunpeng Li, Nan Yu, Yingyao Yu, Hai Long, Rong Xiao, Yuwen Su, Yaping Li, Guiying Zhang, Yixin Tan, Haijing Wu, Qianjin Lu","doi":"10.1111/exd.15082","DOIUrl":"https://doi.org/10.1111/exd.15082","url":null,"abstract":"<p>As a chronic relapsing disease, psoriasis is characterized by widespread skin lesions. The Psoriasis Area and Severity Index (PASI) is the most frequently utilized tool for evaluating the severity of psoriasis in clinical practice. Nevertheless, long-term monitoring and precise evaluation pose difficulties for dermatologists and patients, which is time-consuming, subjective and prone to evaluation bias. To develop a deep learning system with high accuracy and speed to assist PASI evaluation, we collected 2657 high-quality images from 1486 psoriasis patients, and images were segmented and annotated. Then, we utilized the YOLO-v4 algorithm to establish the model via four modules, we also conducted a human-computer comparison through quadratic weighted Kappa (QWK) coefficients and intra-class correlation coefficients (ICC). The YOLO-v4 algorithm was selected for model training and optimization compared with the YOLOv3, RetinaNet, EfficientDet and Faster_rcnn. The model evaluation results of mean average precision (mAP) for various lesion features were as follows: erythema, mAP = 0.903; scale, mAP = 0.908; and induration, mAP = 0.882. In addition, the results of human-computer comparison also showed a median consistency for the skin lesion severity and an excellent consistency for the area and PASI score. Finally, an intelligent PASI app was established for remote disease assessment and course management, with a pleasurable agreement with dermatologists. Taken together, we proposed an intelligent PASI app based on the image YOLO-v4 algorithm that can assist dermatologists in long-term and objective PASI scoring, shedding light on similar clinical assessments that can be assisted by computers in a time-saving and objective manner.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140648154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jessica Conley, Jay R. Perry, Bruce Ashford, Marie Ranson
{"title":"Ex vivo therapeutic screening of metastatic cSCC: A review of methodological considerations for clinical implementation","authors":"Jessica Conley, Jay R. Perry, Bruce Ashford, Marie Ranson","doi":"10.1111/exd.15089","DOIUrl":"https://doi.org/10.1111/exd.15089","url":null,"abstract":"<p>Cutaneous squamous cell carcinoma (cSCC) is the second most common malignancy worldwide, with most deaths caused by locally advanced and metastatic disease. Treatment of resectable metastases is typically limited to invasive surgery with adjuvant radiotherapy; however, many patients fail to respond and there is minimal data to predict response or propose effective alternatives. Precision medicine could improve this, though genomic biomarkers remain elusive in the high mutational background and genomic complexity of cSCC. A phenotypic approach to precision medicine using patient-derived ex vivo tumour models is gaining favour for its capacity to directly assess biological responses to therapeutics as a functional, predictive biomarker. However, the use of ex vivo models for guiding therapeutic selection has yet to be employed for metastatic cSCC. This review will therefore evaluate the existing experimental models of metastatic cSCC and discuss how ex vivo methods could overcome the shortcomings of these existing models. Disease-specific considerations for a prospective methodological pipeline will also be discussed in the context of precision medicine.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.15089","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140641828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}