Youssef Arkan, Haskali Mohammad B, Gorringe Kylie L
Department of Medicine, The University of Melbourne, Melbourne, VIC 3000, Australia.
The Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, VIC 3000, Australia.
Cancers (Basel). 2021 Nov 9;13(22):5596. doi: 10.3390/cancers13225596.
MOC is a rare histotype of epithelial ovarian cancer, and current management options are inadequate for the treatment of late stage or recurrent disease. A shift towards personalised medicines in ovarian cancer is being observed, with trials targeting specific molecular pathways, however, MOC lags due to its rarity. Theranostics is a rapidly evolving category of personalised medicine, encompassing both a diagnostic and therapeutic approach by recognising targets that are expressed highly in tumour tissue in order to deliver a therapeutic payload. The present review evaluates the protein landscape of MOC in recent immunohistochemical- and proteomic-based research, aiming to identify potential candidates for theranostic application. Fourteen proteins were selected based on cell membrane localisation: HER2, EGFR, FOLR1, RAC1, GPR158, CEACAM6, MUC16, PD-L1, NHE1, CEACAM5, MUC1, ACE2, GP2, and PTPRH. Optimal proteins to target using theranostic agents must exhibit high membrane expression on cancerous tissue with low expression on healthy tissue to afford improved disease outcomes with minimal off-target effects and toxicities. We provide guidelines to consider in the selection of a theranostic target for MOC and suggest future directions in evaluating the results of this review.
黏液性卵巢癌(MOC)是上皮性卵巢癌中一种罕见的组织学类型,目前的治疗方案对晚期或复发性疾病的治疗效果不佳。目前正在观察到卵巢癌治疗向个性化药物的转变,有针对特定分子途径的试验,然而,由于MOC的罕见性,其发展滞后。治疗诊断学是个性化医学中一个快速发展的领域,它通过识别在肿瘤组织中高表达的靶点来实现诊断和治疗,从而传递治疗载荷。本综述评估了近期基于免疫组织化学和蛋白质组学研究的MOC蛋白质图谱,旨在确定治疗诊断应用的潜在候选物。基于细胞膜定位选择了14种蛋白质:HER2、表皮生长因子受体(EGFR)、叶酸受体1(FOLR1)、RAC1、G蛋白偶联受体158(GPR158)、癌胚抗原相关细胞黏附分子6(CEACAM6)、黏蛋白16(MUC16)、程序性死亡受体配体1(PD-L1)、钠氢交换体1(NHE1)、癌胚抗原相关细胞黏附分子5(CEACAM5)、黏蛋白1(MUC1)、血管紧张素转换酶2(ACE2)、糖蛋白2(GP2)和蛋白酪氨酸磷酸酶受体H(PTPRH)。使用治疗诊断药物靶向的最佳蛋白质必须在癌组织上表现出高膜表达,而在健康组织上低表达,以在最小的脱靶效应和毒性的情况下改善疾病结果。我们提供了在选择MOC治疗诊断靶点时应考虑的指导原则,并提出了评估本综述结果的未来方向。