Clinical Applications of Antisense Oligonucleotides in Cancer: A Focus on Glioblastoma

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.