Targeting different signaling pathways with antisense oligonucleotides combination for cancer therapy
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Updated: Feb 9, 2026
Intrathecal Delivery of Antisense Oligonucleotides in the Rat Central Nervous System
Published on: October 29, 2019
1Experimental Chemotherapy Laboratory, Regina Elena Cancer Institute, Rome, Italy. zupi@ifo.it
Abstract:
The evidence that cancer development is a complex and multistep process, characterized by alterations of genes involved in the regulation of proliferation, apoptosis and angiogenesis, has led to development of new therapeutic strategies based on the use of agents able to selectively inhibit key molecules of these pathways. In particular, antisense oligonucleotides (ASOs) have proved their efficacy as targeted therapy in preclinical studies, have been well tolerated and able to modulate target protein expression in clinical studies. Although these agents have shown considerable promise for antitumoral therapy, treatment with ASOs used as single agent does not seem particularly promising because of the multigenic alterations of tumors. Based on these considerations, approaches based on the combination of ASOs targeting oncogenes involved in different molecular pathways have been investigated. Moreover, the role of this novel strategy when integrated with conventional drugs or signaling inhibitors, has been assessed. This review addresses some advances in the ASOs combination and reports the potential application of this strategy for the treatment of human cancer.
Insights
Antisense oligonucleotides (ASOs) show promise for cancer therapy. Combining ASOs with other treatments may improve their effectiveness against complex, multigenic tumors.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Cancer is a complex, multistep process involving genetic alterations.
- Key pathways in cancer include proliferation, apoptosis, and angiogenesis.
- Targeted therapies aim to inhibit specific molecules in these pathways.
Purpose of the Study:
- To review advances in combination strategies using antisense oligonucleotides (ASOs) for cancer treatment.
- To assess the potential of integrated ASO therapies with conventional drugs or signaling inhibitors.
Main Methods:
- Review of preclinical and clinical studies on antisense oligonucleotides (ASOs).
- Investigation of combination approaches involving ASOs targeting multiple oncogenes.
- Assessment of ASO integration with conventional chemotherapy and targeted therapies.
Main Results:
- ASOs have demonstrated efficacy and tolerability in preclinical and clinical settings.
- Single-agent ASO therapy may be limited by the multigenic nature of tumors.
- Combination strategies involving ASOs show potential for enhanced antitumoral effects.
Conclusions:
- Combination therapy with antisense oligonucleotides (ASOs) is a promising strategy for human cancer treatment.
- Integrating ASOs with other agents may overcome limitations of single-agent approaches.
- Further research into ASO combination therapies could lead to improved cancer treatment outcomes.
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