Takahashi Akimasa, Hong Linda, Chefetz Ilana
The Hormel Institute, University of Minnesota, Austin, MN 55912, USA.
Department of Obstetrics and Gynecology, Shiga University of Medical Science, Otsu, Shiga 5202152, Japan.
Cancer Drug Resist. 2020 Dec 22;3(4):1021-1033. doi: 10.20517/cdr.2020.93. eCollection 2020.
Ovarian cancer has the highest mortality rate among gynecologic malignancies. The combination of cytoreductive surgery and chemotherapy is the standard regimen for the treatment of ovarian cancer. The initial treatment is usually effective, but many patients with ovarian cancer experience recurrence, and treatment options for recurrent disease remain challenging. Cancer stem cells (CSCs) are suggested to play an essential role in cancer recurrence after initial chemotherapy. Furthermore, they are of great interest as CSCs may also be involved in chemotherapy susceptibility. Thus, understanding the characteristics and mechanisms by which CSCs display resistance to therapeutic agents is important to design effective cancer treatments. In this review, we describe and discuss current therapeutic regimens for ovarian cancer, as well as the various CSC markers, association between CSCs and disease progression, correlation of CSCs with poor prognosis, enrichment of CSCs in tumor tissues following repeated chemotherapy cycles, activation of major signaling pathways following chemotherapy, and potential inhibitors that suppress these signaling cascades. In addition, clinical trials evaluating novel targeted therapies to overcome chemotherapy resistance will be reviewed. The combination of traditional chemotherapy and CSC-targeted therapy could be an effective and promising anticancer treatment for ovarian cancer. Understanding the biological properties of CSCs and the mechanism of chemotherapy resistance are critical to design and develop new therapeutic strategies to overcome CSC-associated chemotherapy resistance.
卵巢癌在妇科恶性肿瘤中死亡率最高。细胞减灭术和化疗相结合是治疗卵巢癌的标准方案。初始治疗通常有效,但许多卵巢癌患者会复发,而复发性疾病的治疗选择仍然具有挑战性。癌症干细胞(CSCs)被认为在初始化疗后的癌症复发中起重要作用。此外,由于癌症干细胞可能也与化疗敏感性有关,因此它们备受关注。因此,了解癌症干细胞对治疗药物产生抗性的特征和机制对于设计有效的癌症治疗方法很重要。在这篇综述中,我们描述并讨论了卵巢癌的当前治疗方案,以及各种癌症干细胞标志物、癌症干细胞与疾病进展的关联、癌症干细胞与预后不良的相关性、重复化疗周期后肿瘤组织中癌症干细胞的富集、化疗后主要信号通路的激活,以及抑制这些信号级联反应的潜在抑制剂。此外,还将综述评估克服化疗抗性的新型靶向疗法的临床试验。传统化疗与针对癌症干细胞的疗法相结合可能是一种有效且有前景的卵巢癌抗癌治疗方法。了解癌症干细胞的生物学特性和化疗抗性机制对于设计和开发新的治疗策略以克服与癌症干细胞相关的化疗抗性至关重要。