TY - JOUR
T1 - Utilizing Superoxide Dismutase Mimetics to Enhance Radiation Therapy Response While Protecting Normal Tissues
AU - Mapuskar, Kranti A.
AU - Anderson, Carryn M.
AU - Spitz, Douglas R.
AU - Batinic-Haberle, Ines
AU - Allen, Bryan G.
AU - E. Oberley-Deegan, Rebecca
N1 - Funding Information:
Funding: This work was supported by an Oberley Award from the Holden Comprehensive Cancer Center (BGA, KAM), CCSG P30-CA086862 (BGA, DRS), R01 CA182804 (DRS), Gateway for Cancer Research award G-17-1500T32-GM007337 (BGA), Department of Radiation Oncology University of Iowa (CMA, KAM), NIH R01CA178888 (ROD), NIH SP20 GM103480 COBRE (ROD), Fred and Pamela Buffet Cancer Center Support Grant P30CA036727 (ROD). North Carolina Biotechnology BIG Award ( #2016-BIG-6518 ) (IBH), Sponsorship Research Agreement between BioMImetix Pharmaceutical and Duke University, SPS 186103 (with Ines Batinic-Haberle as PI), DCI NIH Core grant, 5-P30-CA14236-29 (IBH).
Funding Information:
Funding: This work was supported by an Oberley Award from the Holden Comprehensive Cancer Center (BGA, KAM), CCSG P30-CA086862 (BGA, DRS), R01 CA182804 (DRS), Gateway for Cancer Research award G-17-1500T32-GM007337 (BGA), Department of Radiation Oncology University of Iowa (CMA, KAM), NIH R01CA178888 (ROD), NIH SP20 GM103480 COBRE (ROD), Fred and Pamela Buffet Cancer Center Support Grant P30CA036727 (ROD). North Carolina Biotechnology BIG Award (#2016-BIG-6518) (IBH), Sponsorship Research Agreement between BioMImetix Pharmaceutical and Duke University, SPS 186103 (with Ines Batinic-Haberle as PI), DCI NIH Core grant, 5-P30-CA14236-29 (IBH).
Publisher Copyright:
© 2018
PY - 2019/1
Y1 - 2019/1
N2 - Symptomatic normal tissue injury is a common side effect following definitive therapeutic radiation and chemotherapy treatment for a variety of malignancies. These cancer therapy related toxicities may occur acutely during treatment resulting in reduced or missed therapy agent administration or after the completion of therapy resulting in significant chronic morbidities that significantly diminish patient quality of life. Radiation and chemotherapy induce the formation of reactive oxygen species (ROS) both in normal tissues and tumor cells. One type of ROS common to both chemotherapy and radiation therapy is the formation of superoxide (O 2•− ). Fortunately, due to metabolic differences between cancer and normal cell metabolism, as well as improved targeting techniques, ROS generation following radiation and chemotherapy is generally greater in cancer cells compared to normal tissues. However, the levels of ROS generated in normal tissues are capable of inducing significant toxicity. Thus, several groups are focusing on metabolism-based approaches to mitigate normal tissue effects occurring both during and following cancer therapy. This review will summarize the most current preclinical and clinical data available demonstrating the efficacy of small molecule, superoxide dismutase mimetics in minimizing radiation and chemotherapy-induced normal tissue injury, resulting in enhanced patient outcomes.
AB - Symptomatic normal tissue injury is a common side effect following definitive therapeutic radiation and chemotherapy treatment for a variety of malignancies. These cancer therapy related toxicities may occur acutely during treatment resulting in reduced or missed therapy agent administration or after the completion of therapy resulting in significant chronic morbidities that significantly diminish patient quality of life. Radiation and chemotherapy induce the formation of reactive oxygen species (ROS) both in normal tissues and tumor cells. One type of ROS common to both chemotherapy and radiation therapy is the formation of superoxide (O 2•− ). Fortunately, due to metabolic differences between cancer and normal cell metabolism, as well as improved targeting techniques, ROS generation following radiation and chemotherapy is generally greater in cancer cells compared to normal tissues. However, the levels of ROS generated in normal tissues are capable of inducing significant toxicity. Thus, several groups are focusing on metabolism-based approaches to mitigate normal tissue effects occurring both during and following cancer therapy. This review will summarize the most current preclinical and clinical data available demonstrating the efficacy of small molecule, superoxide dismutase mimetics in minimizing radiation and chemotherapy-induced normal tissue injury, resulting in enhanced patient outcomes.
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U2 - 10.1016/j.semradonc.2018.10.005
DO - 10.1016/j.semradonc.2018.10.005
M3 - Review article
C2 - 30573187
AN - SCOPUS:85058447114
VL - 29
SP - 72
EP - 80
JO - Seminars in Radiation Oncology
JF - Seminars in Radiation Oncology
SN - 1053-4296
IS - 1
ER -