Department of Obstetrics and Gynecology, University of Alabama at Birmingham, Birmingham, AL, United States.
University of Alabama at Birmingham School of Medicine, Birmingham, AL, United States.
Gynecol Oncol. 2018 Sep;150(3):569-580. doi: 10.1016/j.ygyno.2018.05.015. Epub 2018 May 27.
Endometrial cancer is the most prevalent gynecologic cancer in the United States. Over the last 10 years, death rates from endometrial cancer have been rising about 1.4% per year. Traditionally endometrial cancer treatment has been driven by stage and histology. Recent studies have, however, shown that cancers of the same stage and histology have very distinct molecular and genomic profiles. Translational research is progressing rapidly and endometrial cancer-specific precision medicine is evolving. The first tissue agnostic therapy based on the molecular profile of the tumor was approved by the FDA this year. The approval of immune checkpoint inhibitor, pembrolizumab (anti-PD-1), for all solid tumors with defective DNA mismatch repair, could benefit 20-30% of patients with advanced endometrial cancer. Other genomic changes and molecular markers in endometrial cancer, such as hormone receptor status, could lead to more tailored therapy in the future. Pre-clinical and clinical investigations of targeted therapies suggest efficacy for some agents. Single agent targeted therapies, however, have modest activity. Identifying biomarkers that effectively determine response to targeted therapy remains a challenge. The next generation of clinical trials will focus on novel combinations and how to best utilize the advances that have been made in sequencing technology and bioinformatics. Although there is currently an immense body of data and many options for obtaining genomic characteristics of endometrial cancer, how to interpret and utilize this data is still being explored. This review will summarize the important trials that have led to the treatment options we have for advanced and/or recurrent endometrial cancer and discuss the important studies that have led to a better understanding of the distinctive molecular and genomic profiles within endometrial cancer. We will review the current status of biomarker-driven targeted therapy in endometrial cancer and the rationale behind ongoing clinical trials that are utilizing novel targeted agents.
子宫内膜癌是美国最常见的妇科癌症。在过去的 10 年中，子宫内膜癌的死亡率每年上升约 1.4%。传统上，子宫内膜癌的治疗方法是根据分期和组织学来决定的。然而，最近的研究表明，同一分期和组织学的癌症具有非常不同的分子和基因组特征。转化研究正在迅速推进，子宫内膜癌的精准医学也在不断发展。今年，FDA 批准了第一种基于肿瘤分子谱的组织不可知治疗方法。免疫检查点抑制剂 pembrolizumab（抗 PD-1）在所有具有缺陷 DNA 错配修复的实体瘤中的批准，可能使 20-30%的晚期子宫内膜癌患者受益。子宫内膜癌中的其他基因组改变和分子标志物，如激素受体状态，可能会导致未来更有针对性的治疗。针对靶向治疗的临床前和临床研究表明，一些药物具有疗效。然而，单一药物靶向治疗的活性较低。确定能有效确定对靶向治疗反应的生物标志物仍然是一个挑战。下一代临床试验将集中在新的联合治疗方法上，并探讨如何最好地利用测序技术和生物信息学方面的进展。尽管目前有大量的数据和许多获得子宫内膜癌基因组特征的选择，但如何解释和利用这些数据仍在探索之中。这篇综述将总结导致我们对晚期和/或复发性子宫内膜癌的治疗选择的重要试验，并讨论导致我们更好地了解子宫内膜癌内部独特的分子和基因组特征的重要研究。我们将回顾目前在子宫内膜癌中基于生物标志物的靶向治疗的现状以及正在进行的临床试验的基本原理，这些试验利用了新型靶向药物。
