Wang Qiongying, Zhang Chan, Liu Shijia, Li Wangshu, Wei Wenjuan, Aziz Aziz Ur Rehman, Lu Han, Wang Daqing
Key Laboratory for Early Diagnosis and Biotherapy of Malignant Tumors in Children and Women, Dalian Women and Children's Medical Group, Dalian, Liaoning, China.
Dalian Medical University, Dalian, Liaoning, China.
J Med Virol. 2025 Aug;97(8):e70564. doi: 10.1002/jmv.70564.
Cervical cancer, a prevalent gynecological malignancy, is primarily associated with human papillomavirus (HPV) infection. However, some cases display distinct molecular alterations beyond HPV, significantly impacting the tumor immune microenvironment (TIME) and posing therapeutic challenges. Among these molecular changes, NTRK gene fusions have emerged as critical drivers of tumor progression, invasiveness, and poor prognosis. This review highlights the role of NTRK fusions in cervical cancer oncogenesis, examining their effects on cellular signaling pathways and their interplay with HPV status in shaping TIME. The relationship between HPV infection and NTRK fusions is explored, revealing their combined influence on disease progression. Additionally, the potential of NTRK-targeted therapies in precision oncology is discussed, emphasizing their promise as treatment options for cervical cancer. By addressing the molecular, immune, and clinical complexities of cervical cancer, this review provides valuable insights into advancing research and therapeutic strategies.
宫颈癌是一种常见的妇科恶性肿瘤，主要与人乳头瘤病毒（HPV）感染相关。然而，一些病例显示出除HPV之外的独特分子改变，这对肿瘤免疫微环境（TIME）产生了重大影响，并带来了治疗挑战。在这些分子变化中，神经营养酪氨酸激酶（NTRK）基因融合已成为肿瘤进展、侵袭性和不良预后的关键驱动因素。本综述重点介绍了NTRK融合在宫颈癌发生中的作用，研究了它们对细胞信号通路的影响以及在塑造TIME过程中与HPV状态的相互作用。探讨了HPV感染与NTRK融合之间的关系，揭示了它们对疾病进展的综合影响。此外，还讨论了NTRK靶向治疗在精准肿瘤学中的潜力，强调了它们作为宫颈癌治疗选择的前景。通过解决宫颈癌的分子、免疫和临床复杂性问题，本综述为推进研究和治疗策略提供了有价值的见解。
