Turning on the Radio: Epigenetic Inhibitors as Potential Radiopriming Agents
First introduced during the late 1800s, radiation therapy is fundamental to the treatment of cancer. In developed countries, approximately 60% of all patients receive radiation therapy (also known as the sixty percenters), which makes radioresistance in cancer an important and, to date, unsolved, cl...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2016-07-01
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| Series: | Biomolecules |
| Subjects: | |
| Online Access: | http://www.mdpi.com/2218-273X/6/3/32 |
| _version_ | 1819090940328935424 |
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| author | Bryan Oronsky Jan Scicinski Michelle M. Kim Pedro Cabrales Michael E. Salacz Corey A. Carter Neil Oronsky Harry Lybeck Michelle Lybeck Christopher Larson Tony R. Reid Arnold Oronsky |
| author_facet | Bryan Oronsky Jan Scicinski Michelle M. Kim Pedro Cabrales Michael E. Salacz Corey A. Carter Neil Oronsky Harry Lybeck Michelle Lybeck Christopher Larson Tony R. Reid Arnold Oronsky |
| author_sort | Bryan Oronsky |
| collection | DOAJ |
| description | First introduced during the late 1800s, radiation therapy is fundamental to the treatment of cancer. In developed countries, approximately 60% of all patients receive radiation therapy (also known as the sixty percenters), which makes radioresistance in cancer an important and, to date, unsolved, clinical problem. Unfortunately, the therapeutic refractoriness of solid tumors is the rule not the exception, and the ubiquity of resistance also extends to standard chemotherapy, molecularly targeted therapy and immunotherapy. Based on extrapolation from recent clinical inroads with epigenetic agents to prime refractory tumors for maximum sensitivity to concurrent or subsequent therapies, the radioresistant phenotype is potentially reversible, since aberrant epigenetic mechanisms are critical contributors to the evolution of resistant subpopulations of malignant cells. Within the framework of a syllogism, this review explores the emerging link between epigenetics and the development of radioresistance and makes the case that a strategy of pre- or co-treatment with epigenetic agents has the potential to, not only derepress inappropriately silenced genes, but also increase reactive oxygen species production, resulting in the restoration of radiosensitivity. |
| first_indexed | 2024-12-21T22:31:48Z |
| format | Article |
| id | doaj.art-71367208fbdc4d1b968bb51965282064 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-12-21T22:31:48Z |
| publishDate | 2016-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-71367208fbdc4d1b968bb519652820642022-12-21T18:48:04ZengMDPI AGBiomolecules2218-273X2016-07-01633210.3390/biom6030032biom6030032Turning on the Radio: Epigenetic Inhibitors as Potential Radiopriming AgentsBryan Oronsky0Jan Scicinski1Michelle M. Kim2Pedro Cabrales3Michael E. Salacz4Corey A. Carter5Neil Oronsky6Harry Lybeck7Michelle Lybeck8Christopher Larson9Tony R. Reid10Arnold Oronsky11EpicentRx, Inc, Mountain View, CA 94040, USAEpicentRx, Inc, Mountain View, CA 94040, USADepartment of Radiation Oncology, University of Michigan, Ann Arbor, MI 48109, USADepartment of Bioengineering UCSD, La Jolla, San Diego, CA 92093, USAKU Medical Center, Kansas University, Kansas City, KS 66160, USAMurtha Cancer Center, Walter Reed National Military Medical Center, Bethesda, MD 20889, USACFLS Data, Mountain View, CA 94040, USADepartment of Physiology, Helsinki University, 00100 Helsinki, FinlandEpicentRx, Inc, Mountain View, CA 94040, USAMoores Cancer Center, UCSD, La Jolla, CA 92093, USAMoores Cancer Center, UCSD, La Jolla, CA 92093, USAInterWest Partners, Menlo Park, CA 94025, USAFirst introduced during the late 1800s, radiation therapy is fundamental to the treatment of cancer. In developed countries, approximately 60% of all patients receive radiation therapy (also known as the sixty percenters), which makes radioresistance in cancer an important and, to date, unsolved, clinical problem. Unfortunately, the therapeutic refractoriness of solid tumors is the rule not the exception, and the ubiquity of resistance also extends to standard chemotherapy, molecularly targeted therapy and immunotherapy. Based on extrapolation from recent clinical inroads with epigenetic agents to prime refractory tumors for maximum sensitivity to concurrent or subsequent therapies, the radioresistant phenotype is potentially reversible, since aberrant epigenetic mechanisms are critical contributors to the evolution of resistant subpopulations of malignant cells. Within the framework of a syllogism, this review explores the emerging link between epigenetics and the development of radioresistance and makes the case that a strategy of pre- or co-treatment with epigenetic agents has the potential to, not only derepress inappropriately silenced genes, but also increase reactive oxygen species production, resulting in the restoration of radiosensitivity.http://www.mdpi.com/2218-273X/6/3/32radiotherapyradiosensitizationepigeneticsDNA methyltransferase inhibitionhistone deacetylase inhibitionepigenetic primingreactive oxygen species (ROS) |
| spellingShingle | Bryan Oronsky Jan Scicinski Michelle M. Kim Pedro Cabrales Michael E. Salacz Corey A. Carter Neil Oronsky Harry Lybeck Michelle Lybeck Christopher Larson Tony R. Reid Arnold Oronsky Turning on the Radio: Epigenetic Inhibitors as Potential Radiopriming Agents Biomolecules radiotherapy radiosensitization epigenetics DNA methyltransferase inhibition histone deacetylase inhibition epigenetic priming reactive oxygen species (ROS) |
| title | Turning on the Radio: Epigenetic Inhibitors as Potential Radiopriming Agents |
| title_full | Turning on the Radio: Epigenetic Inhibitors as Potential Radiopriming Agents |
| title_fullStr | Turning on the Radio: Epigenetic Inhibitors as Potential Radiopriming Agents |
| title_full_unstemmed | Turning on the Radio: Epigenetic Inhibitors as Potential Radiopriming Agents |
| title_short | Turning on the Radio: Epigenetic Inhibitors as Potential Radiopriming Agents |
| title_sort | turning on the radio epigenetic inhibitors as potential radiopriming agents |
| topic | radiotherapy radiosensitization epigenetics DNA methyltransferase inhibition histone deacetylase inhibition epigenetic priming reactive oxygen species (ROS) |
| url | http://www.mdpi.com/2218-273X/6/3/32 |
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