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Research is ongoing to clarify how interleukin-12, interleukin-23, and interleukin-17 influence cancer, either promoting or inhibiting tumor development. This review evaluates their potential role in skin tumor development and the safety of pathway inhibitors, with emphasis on melanoma and non-melanoma skin cancer risk.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/research-report/","Research & 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risk of skin malignancies: a review  \nMarta Krzysztofik1, Paweł Brzewski1,2, Aleksandra Kulbat3,4, Magdalena Masajada1,2, Karolina Richter2, Wojciech M. Wysocki2,3,4  \n1Department of Dermatology and Venereology, Stefan Zeromski Municipal Hospital, Krakow, Poland 2 Faculty of Medicine and Health Sciences, Andrzej Frycz Modrzewski Krakow University, Krakow, Poland 3Department of Oncological Surgery, 5th Military Clinical Hospital, Krakow, Poland  \n4 National Institute of Oncology, Maria Sklodowska-Curie Memorial, Warsaw, Poland  \nAdv Dermatol Allergol 2024; XLI (6): 552–559 DOI: [https://doi.org/10.5114/ada.2024.143428](https://doi.org/10.5114/ada.2024.143428)  \nAbstract  \nPsoriasis and psoriatic arthritis are chronic inflammatory conditions that constitute a significant global health burden due to their prevalence and impact on quality of life. A deeper comprehension of psoriasis and psoriatic arthritis pathogenesis has recently led to the emergence of novel classes of biologics targeting the IL-23/Th17 pathway. The specific role of interleukin-12, -23, and-17 in cancer as either promoters or inhibitors is under investigation in various studies. Here, we explore the potential role of interleukin-12, -23, and-17 in the development of skin tumours as well as the safety of using their inhibitors in the treatment of psoriasis and psoriatic arthritis, particularly in relation to the risk of melanoma and non-melanoma skin cancer (NMSC) development.  \nKey words: psoriasis, psoriatic arthritis, melanoma, skin cancer, biologics, targeted therapies.  \nIntroduction  \nPsoriasis is an immune-mediated skin disorder with a prevalence of 2% in Europe and North America [1] . People suffering from psoriasis are at increased risk of developing additional serious conditions such as cardiometabolic diseases, malignancies or depression. Moreover, approximately 20% of patients with psoriasis will develop psoriatic arthritis at some point in their lifetime [2] . For mild cases of psoriasis, the main treatment approach involves topical therapy, whereas patients with moderate to severe psoriasis necessitate more advanced treatment options like phototherapy, retinoids, or traditional immunosuppressants [3] . Nevertheless, a significant number of individuals with psoriasis experience inadequate treatment outcomes with initial systemic therapies or have to discontinue therapy due to adverse events associated with treatment or comorbidities.  \nOne of the major advancements in the treatment of psoriasis was the introduction of biologic agents. This breakthrough stemmed from understanding the disease’s pathogenesis, which involves immune system dysregulation leading to uncontrolled proliferation and abnormal differentiation of keratinocytes. Primarily, the discovery that the development of psoriatic plaques  \nmight be triggered by cytotoxic T lymphocytes producing effector cytokines (interferon γ (IFN-γ) and tumor necrosis factor α (TNF-α)) prompted the utilization of TNF-α inhibitors (like infliximab, adalimumab, etanercept, certolizumab pegol) in treating psoriasis [4, 5] . Following this, the identification of T helper 17 (Th17) cells and their secretion of interleukin-17 (IL-17) and IL-22 emerged as additional crucial factors in the development of psoriasis by triggering the epidermal changes [6, 7] . Upstream of this process, dendritic cells secrete IL-23 to stimulate the differentiation and proliferation of Th17 cells and IL-12, which induces the production of IFN-γ, required for the development of Th1 immune response [8, 9] . These discoveries have led to the development of new, highly effective generations of biologic drugs – inhibitors of IL-23 and related cytokines (ustekinumab, guselkumab, tildrakizumab, risankizumab) and the inhibitors ofthe IL-17 pathway (secukinumab, ixekizumab, brodalumab, bimekizumab) . With the use of biologics, it is now feasible to achiev","cbCaii68V7J28nSF","https://ap.wps.com/l/cbCaii68V7J28nSF","pdf",179106,"English","# Introduction\n## Pathogenesis and evolution of targeted biologics\n# Safety concerns and cancer risk\n## Melanoma and non-melanoma skin cancer with TNF-α inhibitors\n## Emerging data for IL-23 and IL-17 inhibitors\n# Aim and scope of the review","[{\"question\":\"What is the main focus of this review?\",\"answer\":\"The review examines the IL-23/Th17 pathway inhibitors used for psoriasis and psoriatic arthritis, particularly regarding the risk of melanoma and non-melanoma skin cancer.\"},{\"question\":\"Why are IL-12, IL-23, and IL-17 considered relevant to cancer risk?\",\"answer\":\"Their specific roles in cancer are still under investigation, including whether they act as promoters or inhibitors of tumor development in different studies.\"},{\"question\":\"How do cancer risks differ among biologic treatment classes mentioned in the text?\",\"answer\":\"The text notes that studies show increased melanoma and non-melanoma skin cancer risk in patients treated with TNF-α inhibitors, while meta-analysis suggests lower risk with newer IL-23 and IL-17 inhibitors compared with TNF-α inhibitors.\"}]","The IL-23/Th17 pathway inhibitors in the treatment of psoriasis and the risk of skin malignancies - a review | PDF",1789994872]