Department of Obstetrics and Gynaecology, Division of Gynecologic Oncology, University of Toronto, 700 University Ave, 6th Floor, Toronto, ON, M5G 2M5, Canada.
Division of Gynecologic Oncology, Sunnybrook Health Sciences Centre, 2075 Bayview Ave., Room T2 055, Toronto, ON, Canada, M4N 3M5.
Curr Treat Options Oncol. 2022 Aug;23(8):1121-1134. doi: 10.1007/s11864-022-00993-x. Epub 2022 Jul 6.
The treatment of endometrial cancer has recently undergone a paradigm shift from using traditional clinical-pathologic factors to molecular characterization for prognosis and selection of treatment. Recent approval of pembrolizumab, dostarlimab, and the combination of lenvatinib and pembrolizumab has drastically changed the treatment options and response rate for advanced and recurrent endometrial cancer, especially for DNA mismatch repair-deficient (MMRd) tumors. For p53 abnormal tumors, which have the worst prognosis, there are several new treatment approaches including lenvatinib and pembrolizumab, trastuzumab, and possibly a future role for PARP inhibitors in the homologous recombination deficiency (HRD) p53 abnormal population. In DNA polymerase epsilon-mutated (POLEmut) tumors which have an excellent prognosis, there's a possibility to de-escalate treatment, and in the small chance of recurrence, these tumors may be susceptible to immune checkpoint inhibitors. Further research is needed to better characterize biomarkers for prognosis and identify targeted treatments within the p53 wild-type (p53 WT)/no specific molecular profile (NSMP) cohort. Upcoming studies are evaluating adjuvant treatment by molecular subtype and will determine the next steps for precision medicine in endometrial cancer.
最近，子宫内膜癌的治疗已经从使用传统的临床病理因素转变为分子特征分析，以预测预后和选择治疗方法。最近， pembrolizumab、dostarlimab 以及 lenvatinib 和 pembrolizumab 的联合治疗方案的获批，极大地改变了晚期和复发性子宫内膜癌的治疗选择和反应率，特别是对于 DNA 错配修复缺陷（MMRd）肿瘤。对于预后最差的 p53 异常肿瘤，有几种新的治疗方法，包括 lenvatinib 和 pembrolizumab、trastuzumab，以及 PARP 抑制剂在同源重组缺陷（HRD）p53 异常人群中的未来可能作用。在预后良好的 DNA 聚合酶 epsilon 突变（POLEmut）肿瘤中，有可能降低治疗强度，而且在极微小的复发情况下，这些肿瘤可能对免疫检查点抑制剂敏感。需要进一步研究以更好地描述用于预测预后的生物标志物，并确定 p53 野生型（p53 WT）/无特定分子特征（NSMP）患者群体中的靶向治疗方法。即将进行的研究正在根据分子亚型评估辅助治疗，并将确定子宫内膜癌精准医学的下一步措施。
