AP-HP, Institut du Cerveau, Paris Brain Institute, ICM, Inserm U 1127, CNRS UMR 7225, Hôpitaux Universitaires La Pitié Salpêtrière, Charles Foix, DMU Neurosciences, Service de Neuro-Oncologie-Institut de Neurologie, Sorbonne Université, 75013 Paris, France.
Institut de Recherche Servier, Rue Francis Perrin, 91190 Gif-sur-Yvette, France.
Cells. 2024 Nov 11;13(22):1869. doi: 10.3390/cells13221869.
Antisense oligonucleotides (ASOs) are promising drugs capable of modulating the protein expression of virtually any target with high specificity and high affinity through complementary base pairing. However, this requires a deep understanding of the target sequence and significant effort in designing the correct complementary drug. In addition, ASOs have been demonstrated to be well tolerated during their clinical use. Indeed, they are already used in many diseases due to pathogenic RNAs of known sequences and in several neurodegenerative diseases and metabolic diseases, for which they were given marketing authorizations (MAs) in Europe and the United States. Their use in oncology is gaining momentum with several identified targets, promising preclinical and clinical results, and recent market authorizations in the US. However, many challenges remain for their clinical use in cancer. It seems necessary to take a step back and review our knowledge of ASOs and their therapeutic uses in oncology. The objectives of this review are (i) to summarize the current state of the art of ASOs; (ii) to discuss the therapeutic use of ASOs in cancer; and (iii) to focus on ASO usage in glioblastoma, the challenges, and the perspective ahead.
反义寡核苷酸 (ASO) 是一种很有前途的药物，通过互补碱基配对，能够高度特异性和高亲和力地调节几乎任何靶标的蛋白表达。然而，这需要对靶序列有深入的了解，并需要在设计正确的互补药物方面付出巨大的努力。此外，ASO 在临床应用中已被证明具有良好的耐受性。事实上，由于具有已知序列的致病 RNA，它们已经在许多疾病中得到应用，并且在几种神经退行性疾病和代谢性疾病中，它们已在欧洲和美国获得了上市许可（MA）。它们在肿瘤学中的应用也在不断发展，有几个已确定的靶点，有有前景的临床前和临床结果，并且最近在美国获得了市场许可。然而，ASO 在癌症中的临床应用仍面临许多挑战。似乎有必要退一步，回顾我们对 ASO 及其在肿瘤学中的治疗用途的了解。这篇综述的目的是：(i) 总结 ASO 的最新进展；(ii) 讨论 ASO 在癌症中的治疗用途；(iii) 重点讨论 ASO 在胶质母细胞瘤中的应用、挑战和未来展望。
