Abstract
Systemic delivery of siRNA has the potential to revolutionize cancer therapy. This technology is indifferent to the “druggability” of the target, and therefore opens up opportunities to target cancers driven by mutant RAS genes, or by MYC, β-catenin, and so on. Furthermore, elimination of well-established drug targets such as EGF-R could circumvent the problem of drug resistance. Complex mixtures of siRNAs can be loaded into nanoparticles, facilitating knock-down of genes that confer adaptive resistance, as well as potentiating the effects of knocking down driver genes by eliminating passengers.
In addition to these opportunities, systemic delivery of siRNA has another major advantage, which could greatly accelerate the rate of drug development, while decreasing costs and risk of failure. One a system is proven safe and effective to deliver a specific siRNA or cocktail, the same system can be used repeatedly for different payloads. This is in marked contrast with the current approach of developing individual chemical entities, each with its own safety profile and its own ADME characteristics,
Effective delivery requires nanoparticles with certain physical and chemical properties, but these particles need to be internalized into cells through surface receptors. The physical properties and internalizing ligands add selectivity to the particles, in addition to the expected selectivity of the siRNA payload. Together these considerations raise the possibility of a new generation of safe and effective therapies for treating cancer.
Citation Information: Mol Cancer Ther 2013;12(11 Suppl):CN01-01.
Citation Format: Frank McCormick. Opportunities for systemic treatment using siRNA in nanoparticles. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr CN01-01.
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