{"title":"胆脂瘤:分子发病机制和潜在治疗方向的最新综述。","authors":"Bingwen Xing, Yalong Dang, Kai Xi","doi":"10.2174/0109298673404489250515074316","DOIUrl":null,"url":null,"abstract":"<p><p>Cholesteatoma, an abnormal accumulation of keratinized squamous epithelium in the middle ear, occurs as a locally invasive but histologically benign lesion. Its capacity for bone erosion leads to significant complications, including hearing loss, facial nerve paralysis, and intracranial infections. Chronic inflammation is central to its pathogenesis, with proinflammatory mediators like TNF-α, IL-1β, and IL-6 activating signaling pathways, such as NF-κB, JAK/STAT, and MAPK. These pathways contribute to epithelial hyperproliferation and extracellular matrix degradation mediated by Matrix Metalloproteinases (MMPs). Dysregulation of epithelial cell behavior, involving altered keratinocyte function and reduced E-cadherin-mediated adhesion, may facilitate lesion formation and expansion. Furthermore, aberrant signaling involving growth factors (e.g., EGF, TGF-β) and dysregulation of osteoclast activity via the RANKL pathway contribute to enhanced bone erosion and tissue invasion. Emerging research highlights potential roles of the c-MYC proto-oncogene, microRNAs, and Sonic hedgehog signaling in disease progression, offering deeper insights into the pathogenesis. Current management primarily involves surgical excision, yet high recurrence rates emphasize the need for adjunctive therapeutic strategies. Potential future directions include modulating key pathways, such as NF-κB, MMP activity, and RANKL signaling, as well as exploring interventions related to growth factors and cell adhesion. Integrating molecular insights with clinical research is essential for developing strategies to reduce recurrence and improve patient outcomes.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5000,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Cholesteatoma: An Updated Review of Molecular Pathogenesis and Potential Therapeutic Directions.\",\"authors\":\"Bingwen Xing, Yalong Dang, Kai Xi\",\"doi\":\"10.2174/0109298673404489250515074316\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Cholesteatoma, an abnormal accumulation of keratinized squamous epithelium in the middle ear, occurs as a locally invasive but histologically benign lesion. Its capacity for bone erosion leads to significant complications, including hearing loss, facial nerve paralysis, and intracranial infections. Chronic inflammation is central to its pathogenesis, with proinflammatory mediators like TNF-α, IL-1β, and IL-6 activating signaling pathways, such as NF-κB, JAK/STAT, and MAPK. These pathways contribute to epithelial hyperproliferation and extracellular matrix degradation mediated by Matrix Metalloproteinases (MMPs). Dysregulation of epithelial cell behavior, involving altered keratinocyte function and reduced E-cadherin-mediated adhesion, may facilitate lesion formation and expansion. Furthermore, aberrant signaling involving growth factors (e.g., EGF, TGF-β) and dysregulation of osteoclast activity via the RANKL pathway contribute to enhanced bone erosion and tissue invasion. Emerging research highlights potential roles of the c-MYC proto-oncogene, microRNAs, and Sonic hedgehog signaling in disease progression, offering deeper insights into the pathogenesis. Current management primarily involves surgical excision, yet high recurrence rates emphasize the need for adjunctive therapeutic strategies. Potential future directions include modulating key pathways, such as NF-κB, MMP activity, and RANKL signaling, as well as exploring interventions related to growth factors and cell adhesion. Integrating molecular insights with clinical research is essential for developing strategies to reduce recurrence and improve patient outcomes.</p>\",\"PeriodicalId\":10984,\"journal\":{\"name\":\"Current medicinal chemistry\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":3.5000,\"publicationDate\":\"2025-05-19\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Current medicinal chemistry\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.2174/0109298673404489250515074316\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current medicinal chemistry","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2174/0109298673404489250515074316","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Cholesteatoma: An Updated Review of Molecular Pathogenesis and Potential Therapeutic Directions.
Cholesteatoma, an abnormal accumulation of keratinized squamous epithelium in the middle ear, occurs as a locally invasive but histologically benign lesion. Its capacity for bone erosion leads to significant complications, including hearing loss, facial nerve paralysis, and intracranial infections. Chronic inflammation is central to its pathogenesis, with proinflammatory mediators like TNF-α, IL-1β, and IL-6 activating signaling pathways, such as NF-κB, JAK/STAT, and MAPK. These pathways contribute to epithelial hyperproliferation and extracellular matrix degradation mediated by Matrix Metalloproteinases (MMPs). Dysregulation of epithelial cell behavior, involving altered keratinocyte function and reduced E-cadherin-mediated adhesion, may facilitate lesion formation and expansion. Furthermore, aberrant signaling involving growth factors (e.g., EGF, TGF-β) and dysregulation of osteoclast activity via the RANKL pathway contribute to enhanced bone erosion and tissue invasion. Emerging research highlights potential roles of the c-MYC proto-oncogene, microRNAs, and Sonic hedgehog signaling in disease progression, offering deeper insights into the pathogenesis. Current management primarily involves surgical excision, yet high recurrence rates emphasize the need for adjunctive therapeutic strategies. Potential future directions include modulating key pathways, such as NF-κB, MMP activity, and RANKL signaling, as well as exploring interventions related to growth factors and cell adhesion. Integrating molecular insights with clinical research is essential for developing strategies to reduce recurrence and improve patient outcomes.
期刊介绍:
Aims & Scope
Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews and guest edited thematic issues written by leaders in the field covering a range of the current topics in medicinal chemistry. The journal also publishes reviews on recent patents. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.