RNA interference to enhance radiation therapy: Targeting the DNA damage response

G Ratnayake; A L Bain; N Fletcher; C B Howard; K K Khanna; K J Thurecht

doi:10.1016/j.canlet.2018.09.011

RNA interference to enhance radiation therapy: Targeting the DNA damage response

Cancer Lett. 2018 Dec 28:439:14-23. doi: 10.1016/j.canlet.2018.09.011. Epub 2018 Sep 18.

Authors

G Ratnayake¹, A L Bain², N Fletcher³, C B Howard³, K K Khanna², K J Thurecht⁴

Affiliations

¹ Centre of Advanced Imaging, University of Queensland, Australia; Australian Institute of Bioengineering and Nanotechnology, University of Queensland, Australia; QIMR Berghofer Medical Research Institute, Australia; Royal Brisbane and Women's Hospital, Australia. Electronic address: gishan.ratnayake@gmail.com.
² QIMR Berghofer Medical Research Institute, Australia.
³ Centre of Advanced Imaging, University of Queensland, Australia; Australian Institute of Bioengineering and Nanotechnology, University of Queensland, Australia.
⁴ Centre of Advanced Imaging, University of Queensland, Australia; Australian Institute of Bioengineering and Nanotechnology, University of Queensland, Australia; ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Australia.

PMID: 30240587
DOI: 10.1016/j.canlet.2018.09.011

Abstract

RNA interference (RNAi) therapy is an emerging class of biopharmaceutical that has immense potential in cancer medicine. RNAi medicines are based on synthetic oligonucleotides that can suppress a target protein in tumour cells with high specificity. This review explores the attractive prospect of using RNAi as a radiosensitiser by targeting the DNA damage response. There are a multitude of molecular targets involved in the detection and repair of DNA damage that are suitable for this purpose. Recent developments in delivery technologies such nanoparticle carriers and conjugation strategies have allowed RNAi therapeutics to enter clinical trials in the treatment of cancer. With further progress, RNAi targeting of the DNA damage response may hold great promise in guiding radiation oncology into the era of precision medicine.

Keywords: DNA damage repair; Gene therapy; Nanomedicine; RNA interference; Radiation oncology.

Publication types

Review

MeSH terms

DNA Damage*
Drug Delivery Systems / methods
Gene Expression Regulation, Neoplastic / genetics
Gene Expression Regulation, Neoplastic / radiation effects
Humans
Nanoparticles
Neoplasms / genetics
Neoplasms / radiotherapy*
RNA Interference*
RNA, Small Interfering / administration & dosage
RNA, Small Interfering / genetics
Radiation Tolerance / genetics*

Substances

RNA, Small Interfering