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肿瘤学中的治疗性反义寡核苷酸:从实验台到病床边

Therapeutic Antisense Oligonucleotides in Oncology: From Bench to Bedside.

作者信息

Çakan Elif, Lara Olivia D, Szymanowska Anna, Bayraktar Emine, Chavez-Reyes Arturo, Lopez-Berestein Gabriel, Amero Paola, Rodriguez-Aguayo Cristian

机构信息

Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.

Faculty of Medicine, Hacettepe University, Ankara 06100, Turkey.

出版信息

Cancers (Basel). 2024 Aug 23;16(17):2940. doi: 10.3390/cancers16172940.

DOI:10.3390/cancers16172940
PMID:39272802
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11394571/
Abstract

Advancements in our comprehension of tumor biology and chemoresistance have spurred the development of treatments that precisely target specific molecules within the body. Despite the expanding landscape of therapeutic options, there persists a demand for innovative approaches to address unmet clinical needs. RNA therapeutics have emerged as a promising frontier in this realm, offering novel avenues for intervention such as RNA interference and the utilization of antisense oligonucleotides (ASOs). ASOs represent a versatile class of therapeutics capable of selectively targeting messenger RNAs (mRNAs) and silencing disease-associated proteins, thereby disrupting pathogenic processes at the molecular level. Recent advancements in chemical modification and carrier molecule design have significantly enhanced the stability, biodistribution, and intracellular uptake of ASOs, thereby bolstering their therapeutic potential. While ASO therapy holds promise across various disease domains, including oncology, coronary angioplasty, neurological disorders, viral, and parasitic diseases, our review manuscript focuses specifically on the application of ASOs in targeted cancer therapies. Through a comprehensive examination of the latest research findings and clinical developments, we delve into the intricacies of ASO-based approaches to cancer treatment, shedding light on their mechanisms of action, therapeutic efficacy, and prospects.

摘要

我们对肿瘤生物学和化学抗性理解的进展推动了针对体内特定分子的精准治疗方法的发展。尽管治疗选择的范围不断扩大,但仍需要创新方法来满足未满足的临床需求。RNA疗法已成为该领域一个有前景的前沿领域,为RNA干扰和反义寡核苷酸(ASO)的利用等干预提供了新途径。ASO是一类通用的治疗剂,能够选择性地靶向信使RNA(mRNA)并沉默与疾病相关的蛋白质,从而在分子水平上破坏致病过程。化学修饰和载体分子设计方面的最新进展显著提高了ASO的稳定性、生物分布和细胞内摄取,从而增强了它们的治疗潜力。虽然ASO疗法在包括肿瘤学、冠状动脉血管成形术、神经系统疾病、病毒和寄生虫疾病在内的各种疾病领域都有前景,但我们的综述手稿特别关注ASO在靶向癌症治疗中的应用。通过全面审视最新研究结果和临床进展,我们深入探讨基于ASO的癌症治疗方法的复杂性,阐明其作用机制、治疗效果和前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5569/11394571/8a6cb9ea7704/cancers-16-02940-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5569/11394571/5239d5b05e34/cancers-16-02940-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5569/11394571/fd404b9311bb/cancers-16-02940-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5569/11394571/f73075b59792/cancers-16-02940-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5569/11394571/3beb8060bf34/cancers-16-02940-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5569/11394571/e35d5116e461/cancers-16-02940-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5569/11394571/8a6cb9ea7704/cancers-16-02940-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5569/11394571/5239d5b05e34/cancers-16-02940-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5569/11394571/fd404b9311bb/cancers-16-02940-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5569/11394571/f73075b59792/cancers-16-02940-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5569/11394571/3beb8060bf34/cancers-16-02940-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5569/11394571/e35d5116e461/cancers-16-02940-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5569/11394571/8a6cb9ea7704/cancers-16-02940-g006.jpg

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