A systematic evaluation of the therapeutic potential of endogenous-ADAR editors in cancer prevention and treatment.
| Title: | A systematic evaluation of the therapeutic potential of endogenous-ADAR editors in cancer prevention and treatment. |
|---|---|
| Authors: | Merdler-Rabinowicz R; Cancer Data Science Lab, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, United States.; Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, 5290002, Israel.; The Institute of Nanotechnology and Advanced Materials, Bar-Ilan University, Ramat Gan, 5290002, Israel.; Dadush A; Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, 5290002, Israel.; The Institute of Nanotechnology and Advanced Materials, Bar-Ilan University, Ramat Gan, 5290002, Israel.; Patiyal S; Cancer Data Science Lab, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, United States.; Rajagopal PS; Cancer Data Science Lab, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, United States.; Daya GN; Cancer Data Science Lab, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, United States.; Ben-Aroya S; Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, 5290002, Israel.; Schäffer AA; Cancer Data Science Lab, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, United States.; Eisenberg E; Raymond and Beverly Sackler School of Physics and Astronomy, Tel-Aviv University, Tel Aviv, 6997801, Israel.; Ruppin E; Cancer Data Science Lab, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, United States.; Levanon EY; Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, 5290002, Israel.; The Institute of Nanotechnology and Advanced Materials, Bar-Ilan University, Ramat Gan, 5290002, Israel. |
| Source: | NAR cancer [NAR Cancer] 2025 May 06; Vol. 7 (2), pp. zcaf016. Date of Electronic Publication: 2025 May 06 (Print Publication: 2025). |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Oxford University Press Country of Publication: England NLM ID: 101769553 Publication Model: eCollection Cited Medium: Internet ISSN: 2632-8674 (Electronic) Linking ISSN: 26328674 NLM ISO Abbreviation: NAR Cancer Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Oxford : Oxford University Press, [2019]- |
| MeSH Terms: | Neoplasms*/genetics ; Neoplasms*/prevention & control ; Neoplasms*/therapy ; Adenosine Deaminase*/genetics ; Adenosine Deaminase*/metabolism ; Adenosine Deaminase*/therapeutic use ; RNA-Binding Proteins*/genetics ; RNA Editing*; Humans ; Genetic Predisposition to Disease ; Mutation ; Germ-Line Mutation |
| Abstract: | Adenosine deaminases acting on RNA (ADAR) enzymes constitute a natural cellular mechanism that induces A-to-I(G) editing, introducing genetic changes at the RNA level. Recently, interest in the endogenous-ADAR editor has emerged for correcting genetic mutations, consisting of a programmed oligonucleotide that attracts the native ADAR, thereby offering opportunities for medical therapy. Here, we systematically chart the scope of cancer mutations that endogenous-ADAR can correct. First, analyzing germline single nucleotide variants in cancer predisposition genes, we find that endogenous-ADAR can revert a fifth of them, reducing the risk of cancer development later in life. Second, examining somatic mutations across various cancer types, we find that it has the potential to correct at least one driver mutation in over a third of the samples, suggesting a promising future treatment strategy. We also highlight key driver mutations that are amenable to endogenous-ADAR, and are thus of special clinical interest. As using endogenous-ADAR entails delivering relatively small payloads, the prospects of delivering endogenous-ADAR to various cancers seem promising. We expect that the large scope of correctable mutations that are systematically charted here for the first time will pave the way for a new era of cancer treatment options.; (© The Author(s) 2025. Published by Oxford University Press on behalf of NAR Cancer.) |
| Competing Interests: | None declared. |
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| Substance Nomenclature: | EC 3.5.4.4 (Adenosine Deaminase); EC 3.5.4.37 (ADAR protein, human); 0 (RNA-Binding Proteins) |
| Entry Date(s): | Date Created: 20250507 Date Completed: 20250507 Latest Revision: 20250509 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC12053386 |
| DOI: | 10.1093/narcan/zcaf016 |
| PMID: | 40330550 |
| Database: | MEDLINE |
Journal Article