Journal article
Pharmacological Ascorbate as a Means of Sensitizing Cancer Cells to Radio-Chemotherapy While Protecting Normal Tissue
Seminars in radiation oncology, Vol.29(1), pp.25-32
01/2019
DOI: 10.1016/j.semradonc.2018.10.006
PMCID: PMC6310038
PMID: 30573181
Abstract
Chemoradiation has remained the standard of care treatment for many of the most aggressive cancers. However, despite effective toxicity to cancer cells, current chemoradiation regimens are limited in efficacy due to significant normal cell toxicity. Thus, efforts have been made to identify agents demonstrating selective toxicity, whereby treatments simultaneously sensitize cancer cells to protect normal cells from chemoradiation. Pharmacological ascorbate (intravenous infusions of vitamin C resulting in plasma ascorbate concentrations ≥20 mM; P-AscH
) has demonstrated selective toxicity in a variety of preclinical tumor models and is currently being assessed as an adjuvant to standard-of-care therapies in several early phase clinical trials. This review summarizes the most current preclinical and clinical data available demonstrating the multidimensional role of P-AscH
in cancer therapy including: selective toxicity to cancer cells via a hydrogen peroxide (H
O
)-mediated mechanism; action as a sensitizing agent of cancer cells to chemoradiation; a protectant of normal tissues exposed to chemoradiation; and its safety and tolerability in clinical trials.
Details
- Title: Subtitle
- Pharmacological Ascorbate as a Means of Sensitizing Cancer Cells to Radio-Chemotherapy While Protecting Normal Tissue
- Creators
- Joshua D Schoenfeld - Free Radical and Radiation Biology Program, Department of Radiation Oncology, Iowa City, IAMatthew S Alexander - Free Radical and Radiation Biology Program, Department of Radiation Oncology, Iowa City, IA; Department of Surgery, Iowa City, IATimothy J Waldron - Free Radical and Radiation Biology Program, Department of Radiation Oncology, Iowa City, IA; University of Iowa Carver College of Medicine, Iowa City, IA; The Holden Comprehensive Cancer Center, Iowa City, IAZita A Sibenaller - Free Radical and Radiation Biology Program, Department of Radiation Oncology, Iowa City, IADouglas R Spitz - Free Radical and Radiation Biology Program, Department of Radiation Oncology, Iowa City, IA; University of Iowa Carver College of Medicine, Iowa City, IA; The Holden Comprehensive Cancer Center, Iowa City, IAGarry R Buettner - Free Radical and Radiation Biology Program, Department of Radiation Oncology, Iowa City, IA; University of Iowa Carver College of Medicine, Iowa City, IA; The Holden Comprehensive Cancer Center, Iowa City, IABryan G Allen - Free Radical and Radiation Biology Program, Department of Radiation Oncology, Iowa City, IA; University of Iowa Carver College of Medicine, Iowa City, IA; The Holden Comprehensive Cancer Center, Iowa City, IAJoseph J Cullen - Free Radical and Radiation Biology Program, Department of Radiation Oncology, Iowa City, IA; Department of Surgery, Iowa City, IA; University of Iowa Carver College of Medicine, Iowa City, IA; The Holden Comprehensive Cancer Center, Iowa City, IA; Veterans Affairs Medical Center, Iowa City, IA. Electronic address: joseph-cullen@uiowa.edu
- Resource Type
- Journal article
- Publication Details
- Seminars in radiation oncology, Vol.29(1), pp.25-32
- DOI
- 10.1016/j.semradonc.2018.10.006
- PMID
- 30573181
- PMCID
- PMC6310038
- NLM abbreviation
- Semin Radiat Oncol
- ISSN
- 1053-4296
- eISSN
- 1532-9461
- Publisher
- United States
- Grant note
- T32 CA078586 / NCI NIH HHS T32 CA148062 / NCI NIH HHS P01 CA217797 / NCI NIH HHS I01 BX001318 / BLRD VA T32 GM007337 / NIGMS NIH HHS R01 CA184051 / NCI NIH HHS R01 CA182804 / NCI NIH HHS P30 CA086862 / NCI NIH HHS R01 CA169046 / NCI NIH HHS
- Language
- English
- Date published
- 01/2019
- Academic Unit
- Pathology; Surgery; Radiation Oncology
- Record Identifier
- 9984047621902771
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