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Experimental Dermatology Jan 2021The incidence of cutaneous keratinocyte-derived cancers is increasing globally. Basal cell carcinoma (BCC) is the most common malignancy worldwide, and cutaneous... (Review)
Review
The incidence of cutaneous keratinocyte-derived cancers is increasing globally. Basal cell carcinoma (BCC) is the most common malignancy worldwide, and cutaneous squamous cell carcinoma (cSCC) is the most common metastatic skin cancer. BCC can be classified into subtypes based on the histology, and these subtypes are classified further into low- and high-risk tumors. There is an increasing need to identify new therapeutic strategies for the treatment of unresectable and metastatic cSCC, and for aggressive BCC variants such as infiltrating, basosquamous or morpheaform BCCs. The most important risk factor for BCC and cSCC is solar UV radiation, which causes genetic and epigenetic alterations in keratinocytes. Similar gene mutations are noted already in sun-exposed normal skin emphasizing the role of the alterations in the tumor microenvironment in the progression of cSCC. Early events in cSCC progression are alterations in the composition of basement membrane and dermal extracellular matrix induced by influx of microbes, inflammatory cells and activated stromal fibroblasts. Activated fibroblasts promote inflammation and produce growth factors and proteolytic enzymes, including matrix metalloproteinases (MMPs). Transforming growth factor-β produced by tumor cells and fibroblasts induces the expression of MMPs by cSCC cells and promotes their invasion. Fibroblast-derived keratinocyte growth factor suppresses the malignant phenotype of cSCC cells by inhibiting the expression of several MMPs. These findings emphasize the importance of interplay of tumor and stromal cells in the progression of cSCC and BCC and suggest tumor microenvironment as a therapeutic target in cSCC and aggressive subtypes of BCC.
Topics: Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Fibroblast Growth Factor 7; Fibroblasts; Humans; Keratinocytes; Matrix Metalloproteinases; Skin Neoplasms; Transforming Growth Factor beta; Tumor Microenvironment
PubMed: 32869366
DOI: 10.1111/exd.14183 -
International Journal of Molecular... Jul 2023Skin cancers require a multidisciplinary approach. The updated guidelines introduce new insights into the management of these diseases. Melanoma (MM), the third most... (Review)
Review
Skin cancers require a multidisciplinary approach. The updated guidelines introduce new insights into the management of these diseases. Melanoma (MM), the third most common skin cancer, a malignant melanocytic tumor, which is classified into four major histological subtypes, continues to have the potential to be a lethal disease. The mortality-incidence ratio is higher in Eastern European countries compared to Western European countries, which shows the need for better prevention and early detection in Eastern European countries. Basal cell carcinoma (BCC) and squamous cell carcinoma (cSCC) remain the top two skin cancers, and their incidence continues to grow. The gold standard in establishing the diagnosis and establishing the histopathological subtype in BCC and SCC is a skin biopsy. Sebaceous carcinoma (SeC) is an uncommon and potentially aggressive cutaneous malignancy showing sebaceous differentiation. It accounts for 0.7% of skin cancers and 3-6.7% of cancer-related deaths. Due to the rapid extension to the regional lymph nodes, SeC requires early treatment. The main treatment for sebaceous carcinoma is surgical treatment, including Mohs micrographic surgery, which has the advantage of complete margin evaluation and low recurrence rates. Primary cutaneous lymphomas (PCLs) are a heterogeneous group of lymphoproliferative diseases, with no evidence of extracutaneous determination at the moment of the diagnosis. PCLs have usually a very different evolution, prognosis, and treatment compared to the lymphomas that may secondarily involve the skin. The aim of our review is to summarize the important changes in the approach to treating melanoma, non-melanoma skin, cutaneous T and B cell lymphomas, and other types of skin cancers. For all skin cancers, optimal patient management requires a multidisciplinary approach including dermatology, medical oncology, and radiation oncology.
Topics: Humans; Skin Neoplasms; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Melanoma; Skin
PubMed: 37446352
DOI: 10.3390/ijms241311176 -
Nature Communications Jan 2021We trained and validated risk prediction models for the three major types of skin cancer- basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma-on a... (Observational Study)
Observational Study
We trained and validated risk prediction models for the three major types of skin cancer- basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma-on a cross-sectional and longitudinal dataset of 210,000 consented research participants who responded to an online survey covering personal and family history of skin cancer, skin susceptibility, and UV exposure. We developed a primary disease risk score (DRS) that combined all 32 identified genetic and non-genetic risk factors. Top percentile DRS was associated with an up to 13-fold increase (odds ratio per standard deviation increase >2.5) in the risk of developing skin cancer relative to the middle DRS percentile. To derive lifetime risk trajectories for the three skin cancers, we developed a second and age independent disease score, called DRSA. Using incident cases, we demonstrated that DRSA could be used in early detection programs for identifying high risk asymptotic individuals, and predicting when they are likely to develop skin cancer. High DRSA scores were not only associated with earlier disease diagnosis (by up to 14 years), but also with more severe and recurrent forms of skin cancer.
Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Cross-Sectional Studies; Datasets as Topic; Direct-To-Consumer Screening and Testing; Female; Follow-Up Studies; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Incidence; Longitudinal Studies; Male; Medical History Taking; Melanoma; Middle Aged; Models, Statistical; Neoplasm Recurrence, Local; Odds Ratio; Prospective Studies; Risk Assessment; Risk Factors; Skin; Skin Neoplasms; Surveys and Questionnaires; Ultraviolet Rays; White People
PubMed: 33420020
DOI: 10.1038/s41467-020-20246-5 -
Cancer Mar 2023Although much attention has been devoted to a detailed genomic exposition of cutaneous melanoma, other nonmelanoma skin cancers have also recently been subjected to... (Review)
Review
Although much attention has been devoted to a detailed genomic exposition of cutaneous melanoma, other nonmelanoma skin cancers have also recently been subjected to similar analytical scrutiny. Chief among these are the most common malignancies worldwide: basal cell carcinomas and cutaneous squamous cell carcinomas. In this review, the authors summarize their latest knowledge about the molecular pathways and therapeutic opportunities attendant to these keratinocytic skin cancers. PLAIN LANGUAGE SUMMARY: The most common cancers in the United States arise from skin cells called keratinocytes. Although these tumors are not formally tracked by the National Cancer Institute, it is estimated that there are millions of skin cancers called basal cell carcinomas and squamous cell carcinomas. This article reviews the current recent genetic insights into these tumors and therapeutic opportunities.
Topics: Humans; Skin Neoplasms; Melanoma; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Keratinocytes; Molecular Biology
PubMed: 36645692
DOI: 10.1002/cncr.34635 -
Anais Brasileiros de Dermatologia 2021Currently, pagetoid dyskeratosis is believed to involve an accelerated keratinization process, possibly induced by mechanical trauma. It represents, in almost its...
Currently, pagetoid dyskeratosis is believed to involve an accelerated keratinization process, possibly induced by mechanical trauma. It represents, in almost its totality, incidental histological findings of specific cells, except when it occurs in the hands, where it usually occurs simultaneously with skin lesions and local dyschromia. These are large, rounded keratinocytes, with pale cytoplasm and a pyknotic nucleus surrounded by a clear halo, which can be easily mistaken by other skin diseases. Its etiology is not completely elucidated, and the correct identification of this entity can be of great importance in the differential diagnosis of skin disorders and the understanding of the keratinization process of the epidermis.
Topics: Carcinoma in Situ; Epidermis; Humans; Keratinocytes; Paget Disease, Extramammary; Skin Neoplasms
PubMed: 34083117
DOI: 10.1016/j.abd.2020.12.006 -
Experimental Dermatology Apr 2021The epidermis and skin appendages are maintained by their resident epithelial stem cells, which undergo long-term self-renewal and multilineage differentiation. Upon... (Review)
Review
The epidermis and skin appendages are maintained by their resident epithelial stem cells, which undergo long-term self-renewal and multilineage differentiation. Upon injury, stem cells are activated to mediate re-epithelialization and restore tissue function. During this process, they often mount lineage plasticity and expand their fates in response to damage signals. Stem cell function is tightly controlled by transcription machineries and signalling transductions, many of which derail in degenerative, inflammatory and malignant dermatologic diseases. Here, by describing both well-characterized and newly emerged pathways, we discuss the transcriptional and signalling mechanisms governing skin epithelial homeostasis, wound repair and squamous cancer. Throughout, we highlight common themes underscoring epithelial stem cell plasticity and tissue-level crosstalk in the context of skin physiology and pathology.
Topics: Animals; Cell Differentiation; Cellular Microenvironment; Epithelial Cells; Hair Follicle; Homeostasis; Humans; Mice; Signal Transduction; Skin; Skin Neoplasms; Stem Cells; Wound Healing
PubMed: 33249665
DOI: 10.1111/exd.14247 -
International Journal of Molecular... Jul 2019The gene is a member of the p53/p63/p73 family of transcription factors and plays a critical role in development and homeostasis of squamous epithelium. is transcribed... (Review)
Review
The gene is a member of the p53/p63/p73 family of transcription factors and plays a critical role in development and homeostasis of squamous epithelium. is transcribed as multiple isoforms; ΔNp63α, the predominant p63 isoform in stratified squamous epithelium, is localized to the basal cells and is overexpressed in squamous cell cancers of multiple organ sites, including skin, head and neck, and lung. Further, p63 is considered a stem cell marker, and within the epidermis, ΔNp63α directs lineage commitment. ΔNp63α has been implicated in numerous processes of skin biology that impact normal epidermal homeostasis and can contribute to squamous cancer pathogenesis by supporting proliferation and survival with roles in blocking terminal differentiation, apoptosis, and senescence, and influencing adhesion and migration. ΔNp63α overexpression may also influence the tissue microenvironment through remodeling of the extracellular matrix and vasculature, as well as by enhancing cytokine and chemokine secretion to recruit pro-inflammatory infiltrate. This review focuses on the role of ΔNp63α in normal epidermal biology and how dysregulation can contribute to cutaneous squamous cancer development, drawing from knowledge also gained by squamous cancers from other organ sites that share p63 overexpression as a defining feature.
Topics: Carcinoma, Squamous Cell; Cell Adhesion; Cell Lineage; Cell Movement; Cell Proliferation; Cell Transformation, Neoplastic; Epidermis; Epithelial Cells; Gene Expression Regulation, Neoplastic; Head and Neck Neoplasms; Humans; Lung Neoplasms; Signal Transduction; Skin Neoplasms; Transcription Factors; Tumor Suppressor Proteins
PubMed: 31340447
DOI: 10.3390/ijms20143590 -
Ecotoxicology and Environmental Safety Jun 2024Air pollutants deteriorate the survival environment and endanger human health around the world. A large number of studies have confirmed that air pollution jeopardizes... (Review)
Review
Air pollutants deteriorate the survival environment and endanger human health around the world. A large number of studies have confirmed that air pollution jeopardizes multiple organs, such as the cardiovascular, respiratory, and central nervous systems. Skin is the largest organ and the first barrier that protects us from the outside world. Air pollutants such as particulate matter (PM), polycyclic aromatic hydrocarbons (PAHs), volatile organic compounds (VOCs) will affect the structure and function of the skin and bring about the development of inflammatory skin diseases (atopic dermatitis (AD), psoriasis), skin accessory diseases (acne, alopecia), auto-immune skin diseases (cutaneous lupus erythematosus(CLE) scleroderma), and even skin tumors (melanoma, basal cell carcinoma (BCC), squamous-cell carcinoma (SCC)). Oxidative stress, skin barrier damage, microbiome dysbiosis, and skin inflammation are the pathogenesis of air pollution stimulation. In this review, we summarize the current evidence on the effects of air pollution on skin diseases and possible mechanisms to provide strategies for future research.
Topics: Humans; Air Pollutants; Air Pollution; Oxidative Stress; Particulate Matter; Polycyclic Aromatic Hydrocarbons; Skin; Skin Diseases; Volatile Organic Compounds
PubMed: 38718731
DOI: 10.1016/j.ecoenv.2024.116429 -
JCI Insight May 2020Recent large-scale GWAS and large epidemiologic studies have accelerated the discovery of genes and environmental factors that contribute to the risk of keratinocyte... (Review)
Review
Recent large-scale GWAS and large epidemiologic studies have accelerated the discovery of genes and environmental factors that contribute to the risk of keratinocyte carcinoma (KC), which includes basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). This Review summarizes the genomic regions associated with SCC and BCC risk, examines the genetic overlap between SCC and BCC, and discusses biological pathways involved in SCC and BCC development. Next, we review environmental factors that are associated with KC risk, including those that are shared between SCC and BCC as well as others that associated with only one type of KC. We conclude with a critical appraisal of current research and potential directions for future research.
Topics: Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Gene-Environment Interaction; Humans; Keratinocytes; Risk Factors; Skin Neoplasms
PubMed: 32434987
DOI: 10.1172/jci.insight.134783 -
Neoplasia (New York, N.Y.) Aug 2022Non-melanoma carcinoma has high incidence rates and has two most common subtypes: basal cell carcinoma and squamous cell carcinoma. This type of carcinoma is usually not... (Review)
Review
Non-melanoma carcinoma has high incidence rates and has two most common subtypes: basal cell carcinoma and squamous cell carcinoma. This type of carcinoma is usually not fatal; however, it can destroy sensory organs such as the nose, ears, and lips. The treatment of these injuries using non-invasive methods is thus strongly recommended. Some treatments for non-melanoma carcinoma are already well defined, such as surgery, cryosurgery, curettage and electrode section, and radiotherapy; however, these conventional treatments cause inflammation and scarring. In the non-surgical treatment of non-melanoma carcinoma, the topical administration of chemotherapeutic drugs contributes for an effective treatment with reduced side effects. However, the penetration of anticancer drugs in the deeper layers of the skin is required. Lipid delivery systems (liposomes, solid lipid nanoparticles, nanostructured lipid carriers) have been developed to overcome epidermal barrier of the skin and to allow the drugs to reach tumor cells. These lipid nanoparticles contribute to control the release profile of the loaded chemotherapeutic drugs, maintaining their stability and increasing death of tumor cells. In this review, the characteristics of non-melanoma carcinoma will be discussed, describing the main existing treatments, together with the contribution of lipid delivery systems as an innovative approach to increase the effectiveness of topical therapies for non-melanoma carcinomas.
Topics: Carcinoma; Drug Delivery Systems; Humans; Lipids; Liposomes; Nanoparticles; Skin; Skin Absorption; Skin Neoplasms
PubMed: 35649306
DOI: 10.1016/j.neo.2022.100810