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RAF antisense oligonucleotide as a tumor radiosensitizer

Oncogene volume 22, pages 5876–5884 (2003)Cite this article

Abstract

The RAF-1 serine–threonine kinase plays a central role in signal transduction pathways involved in cell survival and proliferation. The concept of RAF-1-targeted disruption of cell signaling for therapeutic purposes was first advanced in 1989 with the demonstration of tumor growth inhibition in athymic mice and radiosensitization of human squamous carcinoma cells transfected with a vector expressing antisense cDNA. However, the clinical application of antisense strategies has awaited the development of improved antisense oligonucleotide technologies and drug delivery methods. Nuclease-resistant phosphorothioated antisense oligonucleotides have been the focus of pharmaceutical industry attention. In vivo delivery of nuclease-sensitive, natural backbone/phosphodiester oligonucleotides has remained a formidable challenge. Liposomal encapsulation of antisense oligonucleotides protects them from degradation and enhances drug delivery. Here, we review the importance of targeting RAF-1 signaling in cancer therapy and the preclinical and clinical experiences with a liposomal formulation of a nuclease-sensitive, ends-modified antisense RAF oligonucleotide.

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Acknowledgements

The authors acknowledge colleagues and collaborators for their contributions to the published studies reviewed in this report. The limited number of citations included do not reflect all of the pertinent literature in this field. The authors acknowledge support for their research, in part, by grants from the National Institutes of Health (CA74175) and NeoPharm, Inc. The LErafAON clinical studies are sponsored by NeoPharm, Inc.

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    Usha Kasid & Anatoly Dritschilo

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Kasid, U., Dritschilo, A. RAF antisense oligonucleotide as a tumor radiosensitizer. Oncogene 22, 5876–5884 (2003). https://doi.org/10.1038/sj.onc.1206700

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