Amirlatifi Shahrzad, Forouzin Shabnam, Sadati Elahe, Moradpanah Somayeh, Fazeli Ramina, Panahinia Paria, Zarifi Nasim, Rahimi Sania
Vali-E-Asr Reproductive Health Research Center, Family Health Research Institute, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran.
School of Medicine, Urmia University of Medical Sciences, Urmia, Iran.
Med Oncol. 2025 Jun 30;42(8):302. doi: 10.1007/s12032-025-02860-9.
Ovarian cancer is the most lethal gynecologic malignancy, driven by extensive genetic heterogeneity, clonal evolution, and resistance to therapy. Despite advances in treatment, recurrence remains common, highlighting the urgent need for novel therapeutic strategies. Neutrophil extracellular traps (NETs)-web-like DNA-protein complexes released during NETosis-have recently emerged as key facilitators of tumor progression across multiple cancers. However, their role in ovarian cancer remains underexplored. NETs contribute to metastasis, angiogenesis, immune evasion, and chemoresistance, creating a pro-tumorigenic microenvironment. This review identifies critical knowledge gaps in NET-mediated mechanisms in ovarian cancer and introduces, for the first time in this context, the concept of neutrophil hitchhiking, whereby circulating tumor cells exploit neutrophils to enhance metastatic dissemination. We examine molecular pathways driving NETosis and their influence on the tumor microenvironment, highlighting how NET-targeted therapies-including NETosis inhibitors and immune modulators-offer promising avenues to suppress metastasis, restore immune surveillance, and improve treatment outcomes. By illuminating this underexplored axis of neutrophil-tumor interaction, we aim to stimulate research and therapeutic development that could transform ovarian cancer management.
卵巢癌是最致命的妇科恶性肿瘤，由广泛的基因异质性、克隆进化和对治疗的抗性所驱动。尽管治疗取得了进展，但复发仍然很常见，这凸显了对新型治疗策略的迫切需求。中性粒细胞胞外陷阱（NETs）——在NETosis过程中释放的网状DNA-蛋白质复合物——最近已成为多种癌症肿瘤进展的关键促进因素。然而，它们在卵巢癌中的作用仍未得到充分研究。NETs有助于转移、血管生成、免疫逃逸和化疗耐药，从而营造一个促肿瘤微环境。本综述确定了卵巢癌中NET介导机制方面的关键知识空白，并在此背景下首次引入了中性粒细胞搭便车的概念，即循环肿瘤细胞利用中性粒细胞来增强转移扩散。我们研究了驱动NETosis的分子途径及其对肿瘤微环境的影响，强调了包括NETosis抑制剂和免疫调节剂在内的NET靶向疗法如何为抑制转移、恢复免疫监视和改善治疗结果提供了有前景的途径。通过阐明这条未被充分研究的中性粒细胞与肿瘤相互作用轴，我们旨在推动可能改变卵巢癌治疗方式的研究和治疗开发。
