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抑制信号转导与转录激活因子3(STAT3):提高髓母细胞瘤化疗疗效的一种有前景的方法。

Inhibition of STAT3: A promising approach to enhancing the efficacy of chemotherapy in medulloblastoma.

作者信息

Kumar Sachindra, Arwind Dube Aakash, Kumar B Harish, Pandey Samyak, Nayak Raksha, Vithalkar Megh Pravin, Kumar Nitesh, Pai K Sreedhara Ranganath

机构信息

Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education (MAHE), Manipal 576104, India.

Department of Pharmacology and toxicology, National Institute of Pharmaceutical Education and Research, Hajipur, Vaishali-844102, Bihar, India.

出版信息

Transl Oncol. 2024 Aug;46:102023. doi: 10.1016/j.tranon.2024.102023. Epub 2024 Jun 8.

Abstract

Medulloblastoma is a type of brain cancer that primarily affects children. While chemotherapy has been shown to be effective in treating medulloblastoma, the development of chemotherapy resistance remains a challenge. One potential therapeutic approach is to selectively inhibit the inducible transcription factor called STAT3, which is known to play a crucial role in the survival and growth of tumor cells. The activation of STAT3 has been linked to the growth and progression of various cancers, including medulloblastoma. Inhibition of STAT3 has been shown to sensitize medulloblastoma cells to chemotherapy, leading to improved treatment outcomes. Different approaches to STAT3 inhibition have been developed, including small-molecule inhibitors and RNA interference. Preclinical studies have shown the efficacy of STAT3 inhibitors in medulloblastoma, and clinical trials are currently ongoing to evaluate their safety and effectiveness in patients with various solid tumors, including medulloblastoma. In addition, researchers are also exploring ways to optimize the use of STAT3 inhibitors in combination with chemotherapy and identify biomarkers that can predict treatment that will help to develop personalized treatment strategies. This review highlights the potential of selective inhibition of STAT3 as a novel approach for the treatment of medulloblastoma and suggests that further research into the development of STAT3 inhibitors could lead to improved outcomes for patients with aggressive cancer.

摘要

髓母细胞瘤是一种主要影响儿童的脑癌。虽然化疗已被证明对治疗髓母细胞瘤有效,但化疗耐药性的产生仍然是一个挑战。一种潜在的治疗方法是选择性抑制名为信号转导和转录激活因子3(STAT3)的诱导型转录因子,已知该因子在肿瘤细胞的存活和生长中起关键作用。STAT3的激活与包括髓母细胞瘤在内的各种癌症的生长和进展有关。已证明抑制STAT3可使髓母细胞瘤细胞对化疗敏感,从而改善治疗效果。已开发出不同的抑制STAT3的方法,包括小分子抑制剂和RNA干扰。临床前研究已表明STAT3抑制剂在髓母细胞瘤中的疗效,目前正在进行临床试验以评估其在包括髓母细胞瘤在内的各种实体瘤患者中的安全性和有效性。此外,研究人员还在探索优化STAT3抑制剂与化疗联合使用的方法,并确定可预测治疗效果从而有助于制定个性化治疗策略的生物标志物。这篇综述强调了选择性抑制STAT3作为治疗髓母细胞瘤的一种新方法的潜力,并表明对STAT3抑制剂开发的进一步研究可能会改善侵袭性癌症患者的治疗结果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c55/11220551/092b325bad71/ga1.jpg

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