Department of Medical Oncology (452), Radboud University Medical Center, PO 9101, 6500 HB Nijmegen, The Netherlands.
Semin Cancer Biol. 2017 Jun;44:67-71. doi: 10.1016/j.semcancer.2017.04.009. Epub 2017 Apr 24.
Epithelial ovarian cancer is a highly lethal disease, which is usually diagnosed at a late stage with extensive metastases in the abdominal cavity. Ovarian cancer either develops from the ovarian surface epithelium (OSE) or from serous intra-epithelial carcinoma (STIC). Primary therapy consists of debulking surgery and platinum based chemotherapy. The success of debulking surgery depends on surgical skills but also on the gene signature of the tumour. Debulking surgery combined with first line platinum based chemotherapy, frequently leads to complete remission. However, most ovarian cancers relapse. Once the disease has relapsed, the interval between subsequent therapies decreases steadily due to rapid progression and therapy resistance. Research on therapy resistance of ovarian cancer is frequently devoted to genetic alterations in cancer cells, leading to drug inactivation, enhanced DNA repair mechanisms and intracellular pathway derangements. However the knowledge of ovarian cancer stem cells (OCSC) and the role they play in the development of cancer and therapy resistance is sparse. In this review current knowledge on the characteristics of OCSCs and the micro environmental mechanisms leading to the development or activation of OCSCs resulting in ovarian cancer is reviewed. Moreover the role of OCSC in both surgical and systemic therapy resistance and the relation with epithelial mesenchymal transformation (EMT) is discussed, as are micro-environmental signals leading to OCSC or EMT activation.
上皮性卵巢癌是一种高度致命的疾病，通常在晚期诊断，伴有腹腔广泛转移。卵巢癌要么源自卵巢表面上皮（OSE），要么源自浆液性上皮内癌（STIC）。初始治疗包括肿瘤减灭术和铂类为基础的化疗。肿瘤减灭术的成功不仅取决于手术技能，还取决于肿瘤的基因特征。肿瘤减灭术联合一线铂类化疗，常可导致完全缓解。然而，大多数卵巢癌会复发。一旦疾病复发，由于进展迅速和耐药性，后续治疗的间隔时间会稳步缩短。卵巢癌耐药性的研究通常集中在癌细胞的遗传改变上，导致药物失活、增强的 DNA 修复机制和细胞内途径紊乱。然而，关于卵巢癌干细胞（OCSC）的知识以及它们在癌症发展和耐药性中的作用还很匮乏。本综述回顾了 OCSC 的特征以及导致 OCSC 发展或激活从而导致卵巢癌的微环境机制。此外，还讨论了 OCSC 在手术和全身治疗耐药性中的作用，以及与上皮间质转化（EMT）的关系，以及导致 OCSC 或 EMT 激活的微环境信号。
