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融合基因对癌症干细胞和耐药性的影响。

The impact of fusion genes on cancer stem cells and drug resistance.

机构信息

Department of Genetic Engineering, SRM Institute of Science and Technology, Kattankulathur, Kanchipuram, 603203, Tamil Nadu, India.

Faculty of Allied Health Sciences, Chettinad Academy of Research and Education, Kelambakkam, Chennai, 603103, Tamil Nadu, India.

出版信息

Mol Cell Biochem. 2021 Oct;476(10):3771-3783. doi: 10.1007/s11010-021-04203-4. Epub 2021 Jun 7.

Abstract

With ever increasing evidences on the role of fusion genes as the oncogenic protagonists in myriad cancers, it's time to explore if fusion genes can be the next generational drug targets in meeting the current demands of higher drug efficacy. Eliminating cancer stem cells (CSC) has become the current focus; however, we have reached a standstill in drug development owing to the lack of effective strategies to eradicate CSC. We believe that fusion genes could be the novel targets to overcome this limitation. The intriguing feature of fusion genes is that it dominantly impacts every aspect of CSC including self-renewal, differentiation, lineage commitment, tumorigenicity and stemness. Given the clinical success of fusion gene-based drugs in hematological cancers, our attempt to target fusion genes in eradicating CSC can be rewarding. As fusion genes are expressed explicitly in cancer cells, eradicating CSC by targeting fusion genes provides yet an another advantage of negligible patient side effects since normal cells remain unaffected by the drug. We hereby delineate the latest evidences on how fusion genes regulate CSC and drug resistance.

摘要

随着越来越多的证据表明融合基因作为致癌基因在众多癌症中的作用,现在是时候探讨融合基因是否可以成为下一代药物靶点,以满足提高药物疗效的当前需求。消除癌症干细胞(CSC)已成为当前的重点;然而,由于缺乏有效策略来根除 CSC,药物开发已经停滞不前。我们相信融合基因可能是克服这一限制的新靶点。融合基因的一个有趣特征是,它主要影响 CSC 的方方面面,包括自我更新、分化、谱系决定、致瘤性和干性。鉴于基于融合基因的药物在血液癌症中的临床成功,我们尝试靶向融合基因以根除 CSC 可能会有回报。由于融合基因在癌细胞中明确表达,通过靶向融合基因根除 CSC 提供了另一个优势,即药物对正常细胞几乎没有副作用。我们在此阐述了最新的证据,说明融合基因如何调节 CSC 和耐药性。

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