宫颈癌仍然是一个重要的全球公共卫生问题，在临床环境中经常表现出顺铂耐药性。缺氧是宫颈癌的一个特征，在很大程度上导致顺铂耐药。为了评估顺铂对宫颈癌患者的治疗效果并确定对抗顺铂耐药的潜在有效药物，我们利用接受治疗的患者的临床数据建立了缺氧诱导因子-1（HIF-1）相关风险评分（HRRS）模型与顺铂。 Cox 和 LASSO 回归分析用于对患者风险和预后进行分层。通过 qRT-PCR，我们验证了 9 个潜在的预后 HIF-1 基因，这些基因可以成功预测患者和细胞系对顺铂的反应。随后，我们发现 fostamatinib（一种 FDA 批准的脾脏酪氨酸激酶抑制剂）是一种有前景的针对 HRRS 高人群的药物。我们观察到 fostamatinib 的 IC50 值与 HRRS 在宫颈癌细胞系中呈正相关。此外，fostamatinib 在体外和体内对高 HRRS 组表现出有效的抗癌作用。总之，我们开发了一种缺氧相关基因特征，可以预测宫颈癌中的顺铂反应，并确定福斯塔替尼作为耐药病例的潜在新型治疗方法。© 2024 作者。

Cervical cancer remains a significant global public health concern, often exhibits cisplatin resistance in clinical settings. Hypoxia, a characteristic of cervical cancer, substantially contributes to cisplatin resistance. To evaluate the therapeutic efficacy of cisplatin in patients with cervical cancer and to identify potential effective drugs against cisplatin resistance, we established a hypoxia-inducible factor-1 (HIF-1)-related risk score (HRRS) model using clinical data from patients treated with cisplatin. Cox and LASSO regression analyses were used to stratify patient risks and prognosis. Through qRT-PCR, we validated nine potential prognostic HIF-1 genes that successfully predict cisplatin responsiveness in patients and cell lines. Subsequently, we identified fostamatinib, an FDA-approved spleen tyrosine kinase inhibitor, as a promising drug for targeting the HRRS-high group. We observed a positive correlation between the IC50 values of fostamatinib and HRRS in cervical cancer cell lines. Moreover, fostamatinib exhibited potent anticancer effects on high HRRS groups in vitro and in vivo. In summary, we developed a hypoxia-related gene signature that suggests cisplatin response prediction in cervical cancer and identified fostamatinib as a potential novel treatment approach for resistant cases.© 2024 The Authors.