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This comprehensive review analyzes heightened skin cancer incidence associated with immunosuppressants (methotrexate), chemotherapeutics (fludarabine, hydroxyurea), targeted agents (ibrutinib, JAK inhibitors, MAP kinase pathway inhibitors, sonic hedgehog pathway inhibitors) and radiotherapy. It summarizes mechanisms and key associations with basal cell carcinoma, cutaneous squamous cell carcinoma, and melanoma, discusses factors such as dose and age at exposure, and outlines screening and management strategies before and during treatment.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/skin-malignancies-due-to-anti-cancer-therapies/330816/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/skin-malignancies-due-to-anti-cancer-therapies/330816.png","ImageObject",300,407,{"name":92,"@type":93},"Violet","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-27","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":52},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"Which anti-cancer treatments are linked to higher risk of basal cell carcinoma and cutaneous squamous cell carcinoma?","Question",{"text":112,"@type":113},"Methotrexate is associated with basal cell carcinoma and cutaneous squamous cell carcinoma, especially at higher doses. Fludarabine and hydroxyurea, as well as other chemotherapeutic agents, increase non-melanoma skin cancer risk, including cSCC and BCC.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How do targeted therapies such as ibrutinib, JAK inhibitors, and pathway inhibitors relate to skin cancer incidence?",{"text":117,"@type":113},"Ibrutinib and JAK inhibitors are linked to increased incidence of non-melanoma skin cancers and melanoma. MAP kinase pathway inhibitors, including BRAF inhibitors like vemurafenib, are associated with cSCC and second primary melanomas, while sonic hedgehog pathway inhibitors such as vismodegib can lead to cSCC after treatment for BCC.",{"name":119,"@type":110,"acceptedAnswer":120},"Why is screening important for patients receiving anti-cancer therapies and radiotherapy?",{"text":121,"@type":113},"The review emphasizes that different therapies can raise carcinogenic risk over the long term. 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Skin Malignancies Due to Anti-Cancer Therapies. Cancers 2024, 16, 1960. [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)cancers16111960  \nAcademic Editors: Stamatis Gregoriou, Konstantin Krasagakis and Dimitra Koumaki  \nReceived: 9 April 2024  \nRevised: 19 May 2024  \nAccepted: 20 May 2024  \nPublished: 22 May 2024  \nCopyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \n1 Dermatology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; [michela.starace2@unibo.it](michela.starace2@unibo.it) (M.S.); [stephano.cedirian@studio.unibo.it](stephano.cedirian@studio.unibo.it) (S.C.)  \n2 Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna,  \n40138 Bologna, Italy  \n* Correspondence: [luca.rapparini2@studio.unibo.it](luca.rapparini2@studio.unibo.it); Tel.: +39-051-2143677  \nSimple Summary: Anti-cancer treatments often entail a spectrum of adverse effects, and among these, skin cancers have been under significant scrutiny. From traditional immunosuppressants such as methotrexate to chemotherapeutic agents such as fludarabine and hydroxyurea, as well as from new targeted therapies such as ibrutinib and JAK inhibitors to MAP kinase pathway inhibitors and sonic hedgehog pathway inhibitors, each treatment modality poses unique mechanisms of action and associated risks of skin cancer. In addition, the role of radiotherapy in inducing secondary skin cancers underscores the long-term consequences of therapeutic interventions. It is crucial to ascertain whether a specific therapy increases the risk of skin cancer so that appropriate screening measures can be implemented before and during treatment. Our comprehensive review not only investigates various medications and treatment modalities linked with heightened skin cancer risks, elucidating their mechanisms of action and relevant properties, but also proposes effective strategies for managing patients undergoing such therapies.  \nAbstract: Skin cancers involve a significant concern in cancer therapy due to their association with various treatment modalities. This comprehensive review explores the increased risk of skin cancers linked to different anti-cancer treatments, including classic immunosuppressants such as methotrexate (MTX), chemotherapeutic agents such as fludarabine and hydroxyurea (HU), targeted therapies like ibrutinib and Janus Kinase inhibitors (JAKi), mitogen-activated protein kinase pathway (MAPKP) inhibitors, sonic hedgehog pathway (SHHP) inhibitors, and radiotherapy. MTX, a widely used immunosuppressant in different fields, is associated with basal cell carcinoma (BCC), cutaneoussquamous cell carcinoma (cSCC), and cutaneous melanoma (CM), particularly at higher dosages. Fludarabine, HU, and other chemotherapeutic agents increase the risk of non-melanoma skin cancers (NMSCs), including cSCC and BCC. Targeted therapies like ibrutinib and JAKi have been linked to an elevated incidence of NMSCs and CM. MAPKP inhibitors, particularly BRAF inhibitors like vemurafenib, are associated with the development of cSCCs and second primary melanomas (SPMs) . SHHP inhibitors like vismodegib have been linked to the emergence of cSCCs following treatment for BCC. Additionally, radiotherapy carries carcinogenic risks, especially for BCCs, with increased risks, especially with younger age at the moment of exposure. Understanding these risks and implementing appropriate screening is crucial for effectively managing pat","cbCaitLnqMFrsCh0","https://ap.wps.com/l/cbCaitLnqMFrsCh0","pdf",3137662,15,"English","# Review\n## Skin cancer risk across anti-cancer treatments\n## Immunosuppressants and chemotherapy-related risks\n## Targeted therapies and pathway inhibitors\n## Radiotherapy-associated carcinogenic risks\n## Screening and patient management strategies","[{\"question\":\"Which anti-cancer treatments are linked to higher risk of basal cell carcinoma and cutaneous squamous cell carcinoma?\",\"answer\":\"Methotrexate is associated with basal cell carcinoma and cutaneous squamous cell carcinoma, especially at higher doses. Fludarabine and hydroxyurea, as well as other chemotherapeutic agents, increase non-melanoma skin cancer risk, including cSCC and BCC.\"},{\"question\":\"How do targeted therapies such as ibrutinib, JAK inhibitors, and pathway inhibitors relate to skin cancer incidence?\",\"answer\":\"Ibrutinib and JAK inhibitors are linked to increased incidence of non-melanoma skin cancers and melanoma. MAP kinase pathway inhibitors, including BRAF inhibitors like vemurafenib, are associated with cSCC and second primary melanomas, while sonic hedgehog pathway inhibitors such as vismodegib can lead to cSCC after treatment for BCC.\"},{\"question\":\"Why is screening important for patients receiving anti-cancer therapies and radiotherapy?\",\"answer\":\"The review emphasizes that different therapies can raise carcinogenic risk over the long term. Understanding these risks enables implementation of appropriate screening measures before and during treatment to manage patients effectively.\"}]","Skin Malignancies Due to Anti-Cancer Therapies | PDF",1789990270,38]