肿瘤的基因型分型
目前临床决策无法反映染色体倍性、是否存在 KRAS 或 TP53 突变或 HER2/neu 扩增,但是预期肿瘤的分子指纹有利于进行更佳的风险分层,并可能在不远的未来指导治疗或使治疗具有靶向性。[158]Fung-Kee-Fung M, Dodge J, Elit L, et al. Cancer Care Ontario Program in Evidence-based Care Gynecology Cancer Disease Site Group. Follow-up after primary therapy for endometrial cancer: a systematic review. Gynecol Oncol. 2006;101:520-529.http://www.cancercare.on.ca/pdf/pebc4-9s.pdfhttp://www.ncbi.nlm.nih.gov/pubmed/16556457?tool=bestpractice.com癌症基因组图谱 (TCGA) 根据高通量的分子特性描述提出了新的子宫内膜癌分类方法。其中描述了子宫内膜癌的四个亚型:POLE 超级突变、微卫星不稳定超突变、拷贝数低以及拷贝数高。[159]Cancer Genome Atlas Research Network; Kandoth C, Schultz N, Cherniack AD, et al. Integrated genomic characterization of endometrial carcinoma. Nature. 2013;497:67-73.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3704730/http://www.ncbi.nlm.nih.gov/pubmed/23636398?tool=bestpractice.com作者发现子宫内膜样肿瘤的特征性表现为拷贝数变异很少,TP53 几乎没有突变,而 PTEN 和 KRAS 频繁突变,而在浆液性和一小部分子宫内膜样肿瘤中,TP53 频繁突变,并存在大量拷贝数变异和少量的 DNA 甲基化改变。有趣的是,子宫内膜癌和浆液性卵巢癌、基底样乳腺癌和结直肠癌的亚型之间具有共同的基因组特征。PIK3CA 和 AKT 的突变及其相关的信号传导通路有望成为新的靶标。[160]Naumann RW. The role of the phosphatidylinositol 3-kinase (PI3K) pathway in the development and treatment of uterine cancer. Gynecol Oncol. 2011;123:411-420.http://www.ncbi.nlm.nih.gov/pubmed/21903247?tool=bestpractice.com[161]Myers AP, Cantley LC. Targeting a common collaborator in cancer development. Sci Transl Med. 2010;2:48ps45.http://www.ncbi.nlm.nih.gov/pubmed/20826838?tool=bestpractice.com
免疫治疗
可调节免疫系统检查点的新药物(例如派姆单抗,这是一种抗程序性死亡 1 (PD-1) 免疫系统检查点抑制剂)有望治疗伴有错配修复缺乏的肿瘤,因而可能适用于子宫内膜癌的一个亚群。[162]Le DT, Uram JN, Wang H, et al. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med. 2015;372:2509-2520.http://www.ncbi.nlm.nih.gov/pubmed/26028255?tool=bestpractice.com
姑息性治疗
妇科肿瘤学组(GOG)及其他学组进行了多项III期临床试验来研究细胞毒性药物在内膜癌中的治疗作用,但目前仍无标准。[8]McMeekin DS, Filiaci VL, Thigpen JT, et al. The relationship between histology and outcome in advanced and recurrent endometrial cancer patients participating in first-line chemotherapy trials: a Gynecologic Oncology Group study. Gynecol Oncol. 2007;106:16-22.http://www.ncbi.nlm.nih.gov/pubmed/17574073?tool=bestpractice.com[31]Modesitt SC, Tian C, Kryscio R, et al. Impact of body mass index on treatment outcomes in endometrial cancer patients receiving doxorubicin and cisplatin: a Gynecologic Oncology Group study. Gynecol Oncol. 2007;105:59-65.http://www.ncbi.nlm.nih.gov/pubmed/17150247?tool=bestpractice.com[112]Randall ME, Filiaci VL, Muss H, et al. Randomized phase III trial of whole-abdominal irradiation versus doxorubicin and cisplatin chemotherapy in advanced endometrial carcinoma: a Gynecologic Oncology Group Study. J Clin Oncol. 2006;24:36-44.http://jco.ascopubs.org/cgi/content/full/24/1/36http://www.ncbi.nlm.nih.gov/pubmed/16330675?tool=bestpractice.comHER-2/neu以及血管再生在侵袭性晚期内膜癌患者中有重要作用,目前对贝伐单抗之类的研究较多,或已进入美国国家综合癌症网络“优先选择药物”之列。