Potential strategies to ameliorate risk of radiotherapy-induced second malignant neoplasms. (June 2016)

• Record Type: Journal Article
• Authors: Martin, Olga A.; Yin, Xiaoyu; Forrester, Helen B.; Sprung, Carl N.; Martin, Roger F.
• Is Part Of: Seminars in cancer biology. Volume 37/38(2016)
• Page Start: 65
• Page End: 76
• Publication Date: 2016-06
• Subjects: CCL2/MCP1 chemokine (C-C motif) ligand 2/monocyte chemotactic protein 1 -- CHFs chlorohydroxyfuranones -- CMCF 3-chloro-4-(chloromethyl)-5-hydroxy-2(5H)-furanone -- MCA 3, 4-dichloro-5-hydroxy-2(5H)-furanone -- MCF 3-chloro-4-methyl-5-hydroxy-2(5H)-furanone -- MX 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone -- COX2 cyclooxygenase-2 -- CsA cyclosporin A -- Cx-43 connexin 43 -- DAMP damage-associated molecular pattern -- DMSO dimethyl sulfoxide -- EGTA ethylene glycol tetraacetic acid -- GM-CSF granulocyte/macrophage colony stimulating factor -- γ-H2AX phosphorylated histone H2AX -- H&NSCC squamous cell carcinoma in the head and neck region -- cICDH isocitrate dehydrogenase -- IFN-α 2a pegylated interferon alfa-2a -- IGFBP-3 insulin-like growth factor-binding protein 3 -- IL-1 interleukin 1 -- IL1R2 interleukin 1 receptor, type II -- ISO-1 (S, R)-3-(4-hydroxyphenyl)-4, 5-dihydro-5-isoxazole acetic acid methyl ester -- JNK c-Jun N-terminal kinase -- MAPK mitogen-activated protein kinases -- MEK-ERK mitogen-activated protein kinases, or extracellular signal-regulated kinases -- MIF macrophage migration inhibitory factor -- NADPH nicotinamide adenine dinucleotide phosphate -- NCRP the National Council on Radiation Protection and Measurements -- 7-Ni 7-Nitroindazole -- NF-κB nuclear factor-κB -- D-NMMA NG-methyl-d-arginine -- l-NMMA NG-methyl-l-arginine -- l-NNA No-nitro-l-arginine -- NO nitric oxide -- cNOS constitutive nitric oxide synthase -- iNOS inducible nitric oxide synthase -- NSAID nonsteroidal anti-inflammatory drugs -- NSCLC non-small cell lung cancer -- OCDLs oxidative clustered DNA lesions -- PKC protein kinase C -- PTGS2/COX-2 prostaglandin-endoperoxide synthase 2/cyclooxygenase 2 -- cPTIO 2-(4-Carboxyphenyl)-4, 4, 5, 5-tetramethylimidazoline-1-oxyl-3-oxide -- RELA transcription factor p65 or nuclear factor NF-kappa-B p65 subunit -- RIBE radiation-induced bystander effects -- RNS reactive nitrogen species -- ROS reactive oxygen species -- RT radiotherapy -- IMRT intensity modulated radiotherapy -- SABR stereotactic ablative radiotherapy -- SMN second malignant neoplasm -- SOD superoxide dismutase -- STAT3 signal transducer and activator of transcription 3 -- MnSOD manganese superoxide dismutase -- TLR toll-like receptor -- TNFα tumor necrosis factor α -- TGFβ transforming growth factor β -- TPA Phorbol ester 12-O-tetradecanoylphorbol 13-acetate; Second malignant neoplasms -- Radiotherapy -- Radiation-induced bystander effect -- Inflammation -- Radioprotectors -- Antioxidants; Cancer -- Periodicals; Neoplasms -- Periodicals; Review Literature; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.semcancer.2015.12.003
• Languages: English
• ISSNs: 1044-579X

Abstract

Abstract: This review is aimed at the issue of radiation-induced second malignant neoplasms (SMN), which has become an important problem with the increasing success of modern cancer radiotherapy (RT). It is imperative to avoid compromising the therapeutic ratio while addressing the challenge of SMN. The dilemma is illustrated by the role of reactive oxygen species in both the mechanisms of tumor cell kill and of radiation-induced carcinogenesis. We explore the literature focusing on three potential routes of amelioration to address this challenge. An obvious approach to avoiding compromise of the tumor response is the use of radioprotectors or mitigators that are selective for normal tissues. We also explore the opportunities to avoid protection of the tumor by topical/regional radioprotection of normal tissues, although this strategy limits the scope of protection. Finally, we explore the role of the bystander/abscopal phenomenon in radiation carcinogenesis, in association with the inflammatory response. Targeted and non-targeted effects of radiation are both linked to SMN through induction of DNA damage, genome instability and mutagenesis, but differences in the mechanisms and kinetics between targeted and non-targeted effects may provide opportunities to lessen SMN. The agents that could be employed to pursue each of these strategies are briefly reviewed. In many cases, the same agent has potential utility for more than one strategy. Although the parallel problem of chemotherapy-induced SMN shares common features, this review focuses on RT associated SMN. Also, we avoid the burgeoning literature on the endeavor to suppress cancer incidence by use of antioxidants and vitamins either as dietary strategies or supplementation.