Recent Advances in Oligonucleotide Therapeutics in Oncology

Abstract

Cancer is one of the leading causes of death worldwide. Conventional therapies, including surgery, radiation, and chemotherapy have achieved increased survival rates for many types of cancer over the past decades. However, cancer recurrence and/or metastasis to distant organs remain major challenges, resulting in a large, unmet clinical need. Oligonucleotide therapeutics, which include antisense oligonucleotides, small interfering RNAs, and aptamers, show promising clinical outcomes for disease indications such as Duchenne muscular dystrophy, familial amyloid neuropathies, and macular degeneration. While no approved oligonucleotide drug currently exists for any type of cancer, results obtained in preclinical studies and clinical trials are encouraging. Here, we provide an overview of recent developments in the field of oligonucleotide therapeutics in oncology, review current clinical trials, and discuss associated challenges.

Safety Testing of an Antisense Oligonucleotide Intended for Pediatric Indications in the Juvenile Göttingen Minipig, including an Evaluation of the Ontogeny of Key Nucleases

“…Usually 12–24 nucleotides in length, ASOs are designed to hybridize with a specific and complementary mRNA, resulting in inhibition of protein translation [ 1 ]. Currently, more than a dozen RNA-targeting therapeutics are authorized for use, while many others are in development for various indications for which no or limited treatment options are available [ 2 , 3 , 4 ].…”

Chemistry of Peptide-Oligonucleotide Conjugates: A Review

“…After the seminal work on RNA interference (RNAi) [ 12 ], it took over 20 years for the first small interfering RNA (siRNA) therapeutic patisiran (Onpattro ® ) to appear [ 13 ]. To date, the progress in non-clinical and clinical studies with synthetic oligonucleotides has prompted the FDA approval of a total of 12 drugs, whereas over 130 are going through various phases of clinical trials [ 14 , 15 ]. However, despite their huge therapeutic potential, oligonucleotides and their analogs, due to their intrinsic physicochemical characteristics, in most cases face the problem of ineffective transport through the cellular membrane, usually via an endocytotic pathway [ 16 , 17 ].…”

Nanoparticles-Based Oligonucleotides Delivery in Cancer: Role of Zebrafish as Animal Model

“…They are based on chemically synthesized oligonucleotides (ONs) with a single- or double-stranded deoxyribonucleic acid (DNA) or ribonucleic acid (RNA) chain with a specific molecular target. This target can be represented by a specific gene, protein, or a class/family of genes or proteins [ 2 ]. In this context, the various molecular profiling strategies that have recently been introduced in the cancer field of studies have dramatically increased the range of molecular targets [ 3 ].…”

“…Although a significant number of phase III clinical trials based on ONs have already been proposed, aspects related to their efficacy still limit the introduction of ON-based compounds in clinical practice for anticancer treatment [ 2 ]. In particular, further studies are needed to understand better drug delivery strategies for each proposed ON-based compound and to develop in vivo models in which the efficacy and the toxicity of these approaches can be evaluated.…”