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芦可替尼用于抑制JAK/STAT通路以治疗上皮性卵巢癌患者的潜在药物重新利用。

Potential drug repurposing of ruxolitinib to inhibit the JAK/STAT pathway for the treatment of patients with epithelial ovarian cancer.

作者信息

Yunianto Irfan, Currie Margaret, Chitcholtan Kenny, Sykes Peter

机构信息

Department of Obstetrics and Gynaecology, University of Otago, Christchurch, New Zealand.

Department of Biology Education, Universitas Ahmad Dahlan, Indonesia.

出版信息

J Obstet Gynaecol Res. 2023 Nov;49(11):2563-2574. doi: 10.1111/jog.15761. Epub 2023 Aug 10.

Abstract

AIM

This review aimed to describe the potential for therapeutic targeting of the JAK/STAT signaling pathway by repurposing the clinically-approved JAK inhibitor ruxolitinib in the patients with epithelial ovarian cancer (OC) setting.

METHODS

We reviewed publications that focus on the inhibition of the JAK/STAT pathway in hematological and solid malignancies including OC.

RESULTS

Preclinical studies showed that ruxolitinib effectively reduces OC cell viability and metastasis and enhances the anti-tumor activity of chemotherapy drugs. There are a number of recent clinical trials exploring the role of JAK/STAT inhibition in solid cancers including OC. Early results have not adequately supported efficacy in solid tumors. However, there are preclinical data and clinical studies supporting the use of ruxolitinib in combination with both chemotherapy and other targeted drugs in OC setting.

CONCLUSION

Inflammatory conditions and persistent activation of the JAK/STAT pathway are associated with tumourigenesis and chemoresistance, and therapeutic blockade of this pathway shows promising results. For women with OC, clinical investigation exploring the role of ruxolitinib in combination with chemotherapy agents or other targeted therapeutics is warranted.

摘要

目的

本综述旨在描述通过重新利用临床批准的JAK抑制剂芦可替尼,在上皮性卵巢癌(OC)患者中靶向治疗JAK/STAT信号通路的潜力。

方法

我们回顾了专注于抑制包括OC在内的血液系统恶性肿瘤和实体恶性肿瘤中JAK/STAT通路的相关出版物。

结果

临床前研究表明,芦可替尼可有效降低OC细胞活力和转移能力,并增强化疗药物的抗肿瘤活性。最近有多项临床试验在探索JAK/STAT抑制在包括OC在内的实体癌中的作用。早期结果尚未充分支持其在实体瘤中的疗效。然而,有临床前数据和临床研究支持在OC治疗中使用芦可替尼联合化疗和其他靶向药物。

结论

炎症状态和JAK/STAT通路的持续激活与肿瘤发生和化疗耐药相关,对该通路的治疗性阻断显示出有前景的结果。对于OC女性患者,有必要开展临床研究以探索芦可替尼联合化疗药物或其他靶向治疗的作用。

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