Deng Junli, Wang Li, Chen Hongmin, Li Lei, Ma Yiming, Ni Jie, Li Yong
Department of Gynecologic Oncology, Henan Cancer Hospital, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, 450008, China.
Cancer Metastasis Rev. 2013 Dec;32(3-4):535-51. doi: 10.1007/s10555-013-9423-y.
The most common ovarian cancer is epithelial ovarian cancer (EOC) characterised by few early symptoms, widespread peritoneal dissemination and ascites at advanced stages that result in poor prognosis. Despite the recent progress in its management, including surgery and chemotherapy, EOC remains the most lethal gynaecological malignancy in women. Due to the limitations of current therapeutic approaches, many patients die of secondary disease (metastasis). MUC1 is associated with cellular transformation and tumorigenicity and is considered as an attractive therapeutic target for cancer therapy owning to its over-expression in most adenocarcinomas including EOC. Tumour-associated MUC1 plays an important role in EOC metastasis and progression. In neoplastic tissues, MUC1 is underglycosylated and reveals epitopes that are masked in the normal cells. This feature makes it possible to target tumour-associated MUC1 with antibodies, toxins or radionuclides or use a vaccine targeting tumour-associated MUC1 antigen. The shed tumour-associated MUC1 in blood can be used as a diagnostic biomarker for EOC detection and monitoring. Our recent results have shown that over-expression of MUC1 plays a very important role in EOC progression and MUC1 is an ideal target for targeted therapy to control metastatic and recurrent EOC. This review will summarize some important new findings supporting the role of MUC1 in EOC metastasis and progression and focus on the MUC1-based targeted therapy for control of metastatic and recurrent EOC.
最常见的卵巢癌是上皮性卵巢癌(EOC),其特征是早期症状较少,晚期广泛腹膜播散和腹水,导致预后不良。尽管在其治疗方面(包括手术和化疗)取得了近期进展,但EOC仍然是女性中最致命的妇科恶性肿瘤。由于当前治疗方法的局限性,许多患者死于继发性疾病(转移)。MUC1与细胞转化和致瘤性相关,由于其在包括EOC在内的大多数腺癌中过度表达,被认为是癌症治疗的一个有吸引力的治疗靶点。肿瘤相关的MUC1在EOC转移和进展中起重要作用。在肿瘤组织中,MUC1糖基化不足,并暴露在正常细胞中被掩盖的表位。这一特性使得用抗体、毒素或放射性核素靶向肿瘤相关的MUC1或使用靶向肿瘤相关MUC1抗原的疫苗成为可能。血液中脱落的肿瘤相关MUC1可用作EOC检测和监测的诊断生物标志物。我们最近的结果表明,MUC1的过度表达在EOC进展中起非常重要的作用,并且MUC1是控制转移性和复发性EOC的靶向治疗的理想靶点。这篇综述将总结一些支持MUC1在EOC转移和进展中作用的重要新发现,并聚焦于基于MUC1的控制转移性和复发性EOC的靶向治疗。