卵巢癌干细胞的综合概述：与高复发率，潜在机制和治疗机会的相关性。

IF 27.7 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Cancer Pub Date : 2025-05-07 DOI:10.1186/s12943-025-02345-3

Hadi Alizadeh,Parastoo Akbarabadi,Alireza Dadfar,Mohammad Reza Tareh,Bahram Soltani

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引用次数: 0

摘要

卵巢癌是最致命的妇科恶性肿瘤之一，复发率为70-80%，特别是在晚期（III期或IV期）诊断的患者，其5年生存率低于30%。这种复发的一个关键驱动因素是癌症干细胞（CSCs）的存在，它们表现出对化疗的抗性，并具有自我更新、可塑性和肿瘤再生的能力。肿瘤微环境（TME）通过提供营养和氧梯度、细胞外基质（ECM）相互作用、免疫细胞调节和癌症相关成纤维细胞（CAFs）的支持，在维持卵巢癌干细胞（OCSCs）中起着至关重要的作用。CAFs分泌生长因子、细胞因子和ECM成分，创造促肿瘤的生态位，促进CSC的维持、侵袭和化疗耐药。此外，关键信号通路（包括WNT、NOTCH、PI3K/AKT/mTOR、TGF-β、JAK/STAT、Hedgehog、NF-κB和Hippo）的异常调节支持CSC的干性、可塑性、维持和适应性，从而增加其存活和进展。许多针对这些途径的抑制剂在临床前研究中显示出前景。这篇综述讨论了csc介导的卵巢癌复发的分子机制，并强调了新兴的治疗策略。特别强调的是将常规铂或紫杉烷为基础的方案与OCSC抑制剂联合治疗的潜力，以克服化疗耐药，降低复发率，并改善晚期卵巢癌患者的生存结果。

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A comprehensive overview of ovarian cancer stem cells: correlation with high recurrence rate, underlying mechanisms, and therapeutic opportunities.

Ovarian cancer is one of the most lethal gynecological malignancies, with a recurrence rate of 70-80%, particularly in patients diagnosed at advanced stages (stage III or IV), where the five-year survival rate falls below 30%. A key driver of this recurrence is the presence of cancer stem cells (CSCs), which exhibit resistance to chemotherapy and possess the capacity for self-renewal, plasticity, and tumor regeneration. The tumor microenvironment (TME) plays a crucial role in maintaining ovarian cancer stem cells (OCSCs) by providing nutrient and oxygen gradients, extracellular matrix (ECM) interactions, immune cell modulation, and support from cancer-associated fibroblasts (CAFs). CAFs secrete growth factors, cytokines, and ECM components that create a pro-tumorigenic niche, promoting CSC maintenance, invasion, and chemoresistance. Additionally, dysregulation of critical signaling pathways, including WNT, NOTCH, PI3K/AKT/mTOR, TGF-β, JAK/STAT, Hedgehog, NF-κB, and Hippo, supports CSC stemness, plasticity, maintenance, and adaptability, thereby increasing their survival and progression. Numerous inhibitors targeting these pathways have shown promise in preclinical studies. This review discusses the molecular mechanisms underlying CSC-mediated recurrence in ovarian cancer and highlights emerging therapeutic strategies. Particular emphasis is placed on the potential of combination therapies involving routine platinum or taxane based regimens with OCSC inhibitors to overcome chemoresistance, reduce recurrence rates, and improve survival outcomes for patients with advanced-stage ovarian cancer.

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来源期刊

Molecular Cancer 医学-生化与分子生物学

CiteScore

54.90

自引率

2.70%

发文量

224

审稿时长

2 months

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