Peggy and Charles Stephenson Cancer Center, The University of Oklahoma Health Science Center, Oklahoma City, Oklahoma, USA.
Department of Obstetrics and Gynecology, The University of Oklahoma Health Science Center, Oklahoma City, Oklahoma, USA.
FASEB J. 2024 Nov 15;38(21):e70132. doi: 10.1096/fj.202401991R.
Uterine carcinosarcoma (UCS) is a rare and highly aggressive gynecological malignancy characterized by poor prognosis. Due to its rarity, UCS remains relatively unexplored, and specific treatment guidelines are scarce. Despite standard treatments, including surgery, adjuvant chemotherapy, and radiotherapy, UCS has a high recurrence rate and poor overall prognosis. The aggressive nature of UCS is attributed to the metaplastic transformation of carcinomatous elements into sarcoma. This "biphasic" neoplasm features a mixture of epithelial and mesenchymal/tumor components, which partially share molecular signatures and exhibit a typical epithelial-to-mesenchymal transition (EMT) gene expression profile. Recent scientific advancements have highlighted the pivotal role of EMT in UCS progression and mortality. This review covers the epidemiology of UCS, theories regarding its origin, and the current state of clinical trials with more emphasis on the role of EMT drivers in UCS progression and scope of targeting these molecules. By shedding light on the molecular mechanisms supporting UCS, particularly emphasizing the importance of EMT, we aim to provide a more comprehensive understanding of the disease to support the development of more effective therapeutic strategies.
子宫癌肉瘤（UCS）是一种罕见且高度侵袭性的妇科恶性肿瘤，预后较差。由于其罕见性，UCS 的研究相对较少，具体的治疗指南也很少。尽管采用了包括手术、辅助化疗和放疗在内的标准治疗方法，但 UCS 的复发率仍然很高，整体预后较差。UCS 的侵袭性归因于癌性成分向肉瘤的化生转化。这种“双相”肿瘤由上皮和间叶/肿瘤成分混合组成，部分共享分子特征，并表现出典型的上皮-间充质转化（EMT）基因表达谱。最近的科学进展强调了 EMT 在 UCS 进展和死亡率中的关键作用。本综述涵盖了 UCS 的流行病学、起源理论以及临床试验的现状，重点介绍了 EMT 驱动因子在 UCS 进展中的作用以及靶向这些分子的范围。通过阐明支持 UCS 的分子机制，特别是强调 EMT 的重要性，我们旨在更全面地了解该疾病，以支持更有效的治疗策略的发展。
