Abstract:
Uterine leiomyosarcoma (uLMS) is the most common subtype of uterine sarcomas. They have a poor prognosis with high rates of recurrence and metastasis. The five-year survival for uLMS patients is between 25 and 76%, with survival rates approaching 10-15% for patients with metastatic disease at the initial diagnosis. Accumulating evidence suggests that several biological pathways are involved in uLMS pathogenesis. Notably, drugs that block abnormal functions of these pathways remarkably improve survival in uLMS patients. However, due to chemotherapy resistance, there remains a need for novel drugs that can target these pathways effectively. In this review article, we provide an overview of the recent progress in ascertaining the biological functions and regulatory mechanisms in uLMS from the perspective of aberrant biological pathways, including DNA repair, immune checkpoint blockade, protein kinase and intracellular signaling pathways, and the hedgehog pathway. We review the emerging role of epigenetics and epitranscriptome in the pathogenesis of uLMS. In addition, we discuss serum markers, artificial intelligence (AI) combined with machine learning, shear wave elastography, current management and medical treatment options, and ongoing clinical trials for patients with uLMS. Comprehensive, integrated, and deeper insights into the pathobiology and underlying molecular mechanisms of uLMS will help develop novel strategies to treat patients with this aggressive tumor.
摘要:
子宫平滑肌肉瘤(uLMS)是子宫肉瘤最常见的亚型。它们的预后差,复发和转移率高。uLMS患者的五年生存率在25%至76%之间,转移性疾病患者在最初诊断时的生存率接近10-15%。越来越多的证据表明uLMS发病机制涉及几种生物学途径。值得注意的是,阻断这些通路异常功能的药物显著提高了uLMS患者的生存率。然而,由于化疗耐药,仍然需要能够有效靶向这些途径的新药.在这篇评论文章中,我们从异常生物学途径的角度综述了uLMS生物学功能和调控机制的研究进展,包括DNA修复,免疫检查点封锁,蛋白激酶和胞内信号通路,和刺猬路径。我们回顾了表观遗传学和表观基因组在uLMS发病机理中的新兴作用。此外,我们讨论血清标志物,人工智能(AI)与机器学习相结合,剪切波弹性成像,当前的管理和医疗选择,和正在进行的uLMS患者的临床试验。全面,集成,对uLMS的病理生物学和潜在分子机制的更深入了解将有助于开发治疗这种侵袭性肿瘤患者的新策略。