Department of Medical Oncology, Cabrini Health, Malvern, Victoria, Australia.
Faculty of Medicine, Dentistry, and Health Sciences, Monash University, Melbourne, Victoria, Australia.
Cancer. 2022 Mar 15;128(6):1157-1161. doi: 10.1002/cncr.34024. Epub 2021 Dec 7.
Endometrial cancer is common, and a subset recurs and requires additional treatment. Some of these are recognized as being susceptible to immune therapies and are said to have mismatch repair deficiency (dMMR). However, this clinical trial highlights which cases are more likely to respond well: those containing mutations in genes known as Lynch genes and also some with mutations in POLE/POLD1 ("ultra-hypermutation" genes). In contrast, the majority of dMMR endometrial cancers have silencing or DNA methylation of one of these genes, MLH1, and do not seem to be as responsive to single-agent immune therapy. The availability of combination therapies may be important to consider for these women.
子宫内膜癌很常见,其中一部分会复发,需要额外的治疗。其中一些被认为对免疫疗法敏感,并且存在错配修复缺陷(dMMR)。然而,这项临床试验强调了哪些病例更有可能有良好的反应:那些含有 Lynch 基因的基因突变的病例,以及一些含有 POLE/POLD1(“超高频突变”基因)的基因突变的病例。相比之下,大多数 dMMR 子宫内膜癌的这些基因之一(MLH1)存在沉默或 DNA 甲基化,似乎对单一免疫疗法反应不佳。对于这些女性,联合治疗的可用性可能是需要考虑的重要因素。