Radiation Sensitizers

Aparnathi, Mansi K.; Haq, Sami Ul; Allibhai, Zishan; Lok, Benjamin H.; Brade, Anthony M.

doi:10.1007/174_2022_319

Mansi K. Aparnathi²^na1,
Sami Ul Haq³^na1,
Zishan Allibhai^4,5^na1,
Benjamin H. Lok^2,3,5,6^na1 &
…
Anthony M. Brade^5,7^na1

Part of the book series: Medical Radiology ((Med Radiol Radiat Oncol))

332 Accesses

Abstract

Discovery of effective radiosensitization strategies that improve the therapeutic ratio for patients with lung cancer has been a goal of researchers and an area of vigorous investigation for the past several decades. A pure radiosensitizer is a drug, a modality of therapy, or an intervention that, on its own, lacks direct antitumor activity but enhances the cytotoxicity of radiotherapy when employed in combination. In this chapter we outline the previous and ongoing attempts to radiosensitize lung cancers through improved tumor oxygenation, augmentation of the effectiveness of radiotherapy in hypoxic tumor cells, and use of drugs that modulate with DNA repair and apoptosis. To date, no pure radiosensitization strategy has established itself in standard practice but the current research suggests that this field continues to hold great promise for the improvement of outcome in patients with lung cancer.

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References

Abbotts R, Topper MJ, Biondi C et al (2019) DNA methyltransferase inhibitors induce a BRCAness phenotype that sensitizes NSCLC to PARP inhibitor and ionizing radiation. Proc Natl Acad Sci U S A 116:22609–22618. https://doi.org/10.1073/pnas.1903765116
Article Google Scholar
Al Zubaidi T, Gehrisch OHF, Genois MM et al (2021) Targeting the DNA replication stress phenotype of KRAS mutant cancer cells. Sci Rep 11(1):3656. https://doi.org/10.1038/s41598-021-83142-y
Article Google Scholar
Albert JM, Cao C, Kwang WK et al (2007) Inhibition of poly(ADP-ribose) polymerase enhances cell death and improves tumor growth delay in irradiated lung cancer models. Clin Cancer Res 13:3033–3042. https://doi.org/10.1158/1078-0432.CCR-06-2872
Article Google Scholar
Babar IA, Czochor J, Steinmetz A et al (2011) Inhibition of hypoxia-induced miR-155 radiosensitizes hypoxic lung cancer cells. Cancer Biol Ther 12:908–914. https://doi.org/10.4161/cbt.12.10.17681
Article Google Scholar
Bandyopadhyay K, Banères JL, Martin A et al (2009) Spermidinyl-CoA-based HAT inhibitors block DNA repair and provide cancer-specific chemo- and radiosensitization. Cell Cycle 8:2779–2788. https://doi.org/10.4161/cc.8.17.9416
Article Google Scholar
Bauman JR, Edelman MJ (2022) Targeted therapies in non-small cell lung cancer. Med Radiol Radiat Oncol. https://doi.org/10.1007/174_2022_312
Becker A, Hänsgen G, Blocking M et al (1998) Oxygenation of squamous cell carcinoma of the head and neck: comparison of primary tumors, neck node metastases, and normal tissue. Int J Radiat Oncol Biol Phys 42:35–41. https://doi.org/10.1016/S0360-3016(98)00182-5
Article Google Scholar
Bellini MJ, Polo MP, De Alaniz MJT, De Bravo MG (2003) Effect of simvastatin on the uptake and metabolic conversion of palmitic, dihomo-γ-linoleic and α-linolenic acids in A549 cells. Prostaglandins Leukot Essent Fatty Acids 69:351–357. https://doi.org/10.1016/S0952-3278(03)00149-2
Article Google Scholar
Bennett MH, Feldmeier J, Hampson N et al (2005) Hyperbaric oxygen therapy for late radiation tissue injury. Cochrane Database Syst Rev 2016(4):CD005005. https://doi.org/10.1002/14651858.CD005005.pub2
Article Google Scholar
Bernier J, Denekamp J, Rojas A et al (1999) ARCON: accelerated radiotherapy with carbogen and nicotinamide in non-small cell lung cancer: a phase I/II study by the EORTC. Radiother Oncol 52:149–156. https://doi.org/10.1016/S0167-8140(99)00106-1
Article Google Scholar
Bi N, Liang J, Zhou Z et al (2019) Effect of concurrent chemoradiation with celecoxib vs concurrent chemoradiation alone on survival among patients with non-small cell lung cancer with and without cyclooxygenase 2 genetic variants: a phase 2 randomized clinical trial. JAMA Netw Open 2:e1918070. https://doi.org/10.1001/jamanetworkopen.2019.18070
Article Google Scholar
Bohlius J, Schmidlin K, Brillant C et al (2009) Recombinant human erythropoiesis-stimulating agents and mortality in patients with cancer: a meta-analysis of randomised trials. Lancet 373:1532–1542. https://doi.org/10.1016/S0140-6736(09)60502-X
Article Google Scholar
Bridges KA, Toniatti C, Buser CA et al (2014) Niraparib (MK-4827), a novel poly(ADP-ribose) polymerase inhibitor, radiosensitizes human lung and breast cancer cells. Oncotarget 5:5076–5086. https://doi.org/10.18632/oncotarget.2083
Article Google Scholar
Brizel DM, Scully SP, Harrelson JM et al (1996) Tumor oxygenation predicts for the likelihood of distant metastases in human soft tissue sarcoma. Cancer Res 56:941–943
Google Scholar
Brown JM, Giaccia AJ (1998) The unique physiology of solid tumors: opportunities (and problems) for cancer therapy. Cancer Res 58:1408–1416
Google Scholar
Bui QC, Lieber M, Withers HR et al (2004) The efficacy of hyperbaric oxygen therapy in the treatment of radiation-induced late side effects. Int J Radiat Oncol Biol Phys 60:871–878. https://doi.org/10.1016/j.ijrobp.2004.04.019
Article Google Scholar
Chalmers AJ, Lakshman M, Chan N, Bristow RG (2010) Poly(ADP-ribose) polymerase inhibition as a model for synthetic lethality in developing radiation oncology targets. Semin Radiat Oncol 20:274–281. https://doi.org/10.1016/j.semradonc.2010.06.001
Article Google Scholar
Chan N, Pires IM, Bencokova Z et al (2010) Contextual synthetic lethality of cancer cell kill based on the tumor microenvironment. Cancer Res 70:8045–8054. https://doi.org/10.1158/0008-5472.CAN-10-2352
Article Google Scholar
Chen Y, Wang Y, Zhao L et al (2018) EGFR tyrosine kinase inhibitor HS-10182 increases radiation sensitivity in non-small cell lung cancers with EGFR T790M mutation. Cancer Biol Med 15:39–51. https://doi.org/10.20892/j.issn.2095-3941.2017.0118
Article Google Scholar
Cho HJ, Ahn KC, Choi JY et al (2015) Luteolin acts as a radiosensitizer in non-small cell lung cancer cells by enhancing apoptotic cell death through activation of a p38/ROS/caspase cascade. Int J Oncol 46:1149–1158. https://doi.org/10.3892/ijo.2015.2831
Article Google Scholar
Choy H, Nabid A, Stea B et al (2005) Phase II multicenter study of induction chemotherapy followed by concurrent efaproxiral (RSR13) and thoracic radiotherapy for patients with locally advanced non-small-cell lung cancer. J Clin Oncol 23:5918–5928. https://doi.org/10.1200/JCO.2005.08.011
Article Google Scholar
Chung EJ, Brown AP, Asano H et al (2009) In vitro and in vivo radiosensitization with AZD6244 (ARRY-142886), an inhibitor of mitogen-activated protein kinase/extracellular signal-regulated kinase 1/2 kinase. Clin Cancer Res 15:3050–3057. https://doi.org/10.1158/1078-0432.CCR-08-2954
Article Google Scholar
Cuneo KC, Fu A, Osusky K et al (2007) Histone deacetylase inhibitor NVP-LAQ824 sensitizes human nonsmall cell lung cancer to the cytotoxic effects of ionizing radiation. Anticancer Drugs 18:793–800. https://doi.org/10.1097/CAD.0b013e3280b10d57
Article Google Scholar
Dantzer F, De La Rubia G, Ménissier-De Murcia J et al (2000) Base excision repair is impaired in mammalian cells lacking poly(ADP-ribose) polymerase-1. Biochemistry 39:7559–7569. https://doi.org/10.1021/bi0003442
Article Google Scholar
Diederich M, Sobolewski C, Cerella C et al (2010) The role of cyclooxygenase-2 in cell proliferation and cell death in human malignancies. Int J Cell Biol 2010:215158. https://doi.org/10.1155/2010/215158
Article Google Scholar
Eschmann S, Paulsen F, Reimold M et al (2005) Prognostic impact of hypoxia imaging with before radiotherapy. Radiochemistry 46:253–260
Google Scholar
Eschwège F, Sancho-Garnier H, Chassagne D (1997) Results of a European randomized trial of etanidazole combined with radiotherapy in head and neck carcinomas. Int J Radiat Oncol Biol Phys 39:275–281. https://doi.org/10.1016/s0360-3016(97)00327-1
Article Google Scholar
Farías RO, Bortolussi S, Menéndez PR, González SJ (2014) Exploring Boron Neutron Capture Therapy for non-small cell lung cancer. Phys Med 30:888–897. https://doi.org/10.1016/j.ejmp.2014.07.342
Article Google Scholar
Farías RO, Garabalino MA, Ferraris S et al (2015) Toward a clinical application of ex situ boron neutron capture therapy for lung tumors at the RA-3 reactor in Argentina. Med Phys 42:4161–4173. https://doi.org/10.1118/1.4922158
Article Google Scholar
Farris MK, Steber C, Helis C, Blackstock W (2022) Combined radiotherapy and chemotherapy: theoretical considerations and biological premises. Med Radiol Radiat Oncol. https://doi.org/10.1007/174_2022_314
Fok JHL, Ramos-Montoya A, Vazquez-Chantada M et al (2019) AZD7648 is a potent and selective DNA-PK inhibitor that enhances radiation, chemotherapy and olaparib activity. Nat Commun 10:1–15. https://doi.org/10.1038/s41467-019-12836-9
Article Google Scholar
Fyles AW, Milosevic M, Wong R et al (1998) Oxygenation predicts radiation response and survival in patients with cervix cancer. Radiother Oncol 48:149–156. https://doi.org/10.1016/S0167-8140(98)00044-9
Article Google Scholar
Geng L, Cuneo KC, Fu A et al (2006) Histone deacetylase (HDAC) inhibitor LBH589 increases duration of γ-H2AX foci and confines HDAC4 to the cytoplasm in irradiated non-small cell lung cancer. Cancer Res 66:11298–11304. https://doi.org/10.1158/0008-5472.CAN-06-0049
Article Google Scholar
Gong C, Gu R, Jin H et al (2016) Lysyl oxidase mediates hypoxia-induced radioresistance in non-small cell lung cancer A549 cells. Exp Biol Med 241:387–395. https://doi.org/10.1177/1535370215609694
Article Google Scholar
Han Y, Zhang Y, Yang L-h et al (2012) X-radiation inhibits histone deacetylase 1 and 2, upregulates Axin expression and induces apoptosis in non-small cell lung cancer. Radiat Oncol 7:1. https://doi.org/10.1186/1748-717X-7-183
Article Google Scholar
Han ZQ, Liao H, Shi F et al (2017) Inhibition of cyclooxygenase-2 sensitizes lung cancer cells to radiation-induced apoptosis. Oncol Lett 14:5959–5965. https://doi.org/10.3892/ol.2017.6940
Article Google Scholar
Hastak K, Bhutra S, Parry R, Ford JM (2017) Poly (ADP-ribose) polymerase inhibitor, an effective radiosensitizer in lung and pancreatic cancers. Oncotarget 8:26344–26355. https://doi.org/10.18632/oncotarget.15464
Article Google Scholar
He K, Selek U, Barsoumian HB et al (2022) Mechanisms of action of radiotherapy and immunotherapy in lung cancer: Implications for clinical practice. Med Radiol Radiat Oncol. https://doi.org/10.1007/174_2022_315
Hehlgans S, Storch K, Lange I, Cordes N (2013) The novel HDAC inhibitor NDACI054 sensitizes human cancer cells to radiotherapy. Radiother Oncol 109:126–132. https://doi.org/10.1016/j.radonc.2013.08.023
Article Google Scholar
Helleday T, Petermann E, Lundin C et al (2008) DNA repair pathways as targets for cancer therapy. Nat Rev Cancer 8:193–204. https://doi.org/10.1038/nrc2342
Article Google Scholar
Henk JM, Kunkler PB, Smith CW (1977) RADIOTHERAPY AND HYPERBARIC OXYGEN IN HEAD AND NECK CANCER final report of first controlled clinical trial. Lancet 2:101–103. https://doi.org/10.1016/s0140-6736(77)90116-7
Article Google Scholar
Henke M, Laszig R, Rübe C et al (2003) Erythropoietin to treat head and neck cancer patients with anaemia undergoing radiotherapy: randomised, double-blind, placebo-controlled trial. Lancet (London, England) 362:1255–1260. https://doi.org/10.1016/S0140-6736(03)14567-9
Article Google Scholar
Höckel M, Knoop C, Schlenger K et al (1993) Intratumoral pO2 predicts survival in advanced cancer of the uterine cervix. Radiother Oncol 26:45–50. https://doi.org/10.1016/0167-8140(93)90025-4
Article Google Scholar
Hocsak E, Cseh A, Szabo A et al (2014) PARP inhibitor attenuated colony formation can be restored by MAP kinase inhibitors in different irradiated cancer cell lines. Int J Radiat Biol 90:1152–1161. https://doi.org/10.3109/09553002.2014.934927
Article Google Scholar
Hoskin PJ, Rojas AM, Bentzen SM, Saunders MI (2010) Radiotherapy with concurrent carbogen and nicotinamide in bladder carcinoma. J Clin Oncol 28:4912–4918. https://doi.org/10.1200/JCO.2010.28.4950
Article Google Scholar
Hu C, Zhuang W, Qiao Y et al (2019) Effects of combined inhibition of STAT3 and VEGFR2 pathways on the radiosensitivity of non-small-cell lung cancer cells. Onco Targets Ther 12:933–944. https://doi.org/10.2147/OTT.S186559
Article Google Scholar
Janssens GO, Terhaard CH, Doornaert PA et al (2012) Acute toxicity profile and compliance to accelerated radiotherapy plus carbogen and nicotinamide for clinical stage T2-4 laryngeal cancer: results of a phase III randomized trial. Int J Radiat Oncol Biol Phys 82:532–538. https://doi.org/10.1016/j.ijrobp.2010.11.045
Article Google Scholar
Jiang Y, Verbiest T, Devery AM et al (2016) Hypoxia potentiates the radiation-sensitizing effect of olaparib in human non-small cell lung cancer xenografts by contextual synthetic lethality. Int J Radiat Oncol Biol Phys 95:772–781. https://doi.org/10.1016/j.ijrobp.2016.01.035
Article Google Scholar
Kaanders JHAM, Pop LAM, Marres HAM et al (1998) Accelerated radiotherapy with carbogen and nicotinamide (ARCON) for laryngeal cancer. Radiother Oncol 48:115–122. https://doi.org/10.1016/S0167-8140(98)00043-7
Article Google Scholar
Kang JH, Kim W, Kwon TW et al (2016) Plasminogen activator inhibitor-1 enhances radioresistance and aggressiveness of non-small cell lung cancer cells. Oncotarget 7:23961–23974. https://doi.org/10.18632/oncotarget.8208
Article Google Scholar
Kang SH, Bak DH, Chung BY et al (2020) Delphinidin enhances radio-therapeutic effects via autophagy induction and JNK/MAPK pathway activation in non-small cell lung cancer. Korean J Physiol Pharmacol 24:413–422. https://doi.org/10.4196/kjpp.2020.24.5.413
Article Google Scholar
Khanzada UK, Pardo OE, Meier C et al (2006) Potent inhibition of small-cell lung cancer cell growth by simvastatin reveals selective functions of Ras isoforms in growth factor signalling. Oncogene 25:877–887. https://doi.org/10.1038/sj.onc.1209117
Article Google Scholar
Kim KW, Moretti L, Mitchell LR et al (2009a) Combined Bcl-2/mammalian target of rapamycin inhibition leads to enhanced radiosensitization via induction of apoptosis and autophagy in non-small cell lung tumor xenograft model. Clin Cancer Res 15:6096–6105. https://doi.org/10.1158/1078-0432.CCR-09-0589
Article Google Scholar
Kim BM, Won J, Maeng KA et al (2009b) Nimesulide, a selective COX-2 inhibitor, acts synergistically with ionizing radiation against A549 human lung cancer cells through the activation of caspase-8 and caspase-3. Int J Oncol 34:1467–1473
Google Scholar
Kim EH, Park AK, Dong SM et al (2010) Global analysis of CpG methylation reveals epigenetic control of the radiosensitivity in lung cancer cell lines. Oncogene 29:4725–4731. https://doi.org/10.1038/onc.2010.223
Article Google Scholar
Kim JH, Kim IH, Shin JH et al (2013) Sequence-dependent radiosensitization of histone deacetylase inhibitors trichostatin A and SK-7041. Cancer Res Treat 45:334–342. https://doi.org/10.4143/crt.2013.45.4.334
Article Google Scholar
Klein C, Dokic I, Mairani A et al (2017) Overcoming hypoxia-induced tumor radioresistance in non-small cell lung cancer by targeting DNA-dependent protein kinase in combination with carbon ion irradiation. Radiat Oncol 12:1–8. https://doi.org/10.1186/s13014-017-0939-0
Article Google Scholar
Knight RC, Rowley DA, Skolimowski I, Edwards DI (1979) Mechanism of action of nitroimidazole antimicrobial and antitumour radiosensitizing drugs: effects of reduced misonidazole on DNA. Int J Radiat Biol 36:367–377. https://doi.org/10.1080/09553007914551151
Article Google Scholar
Komaki R, Liao Z, Milas L (2004) Improvement strategies for molecular targeting: cyclooxygenase-2 inhibitors as radiosensitizers for non-small cell lung cancer. Semin Oncol 31:47–53. https://doi.org/10.1053/j.seminoncol.2003.12.014
Article Google Scholar
Kriegs M, Kasten-Pisula U, Rieckmann T et al (2010) The epidermal growth factor receptor modulates DNA double-strand break repair by regulating non-homologous end-joining. DNA Repair (Amst) 9:889–897. https://doi.org/10.1016/j.dnarep.2010.05.005
Article Google Scholar
Krstic D, Markovic VM, Jovanovic Z et al (2014) Monte Carlo calculations of lung dose in ORNL phantom for boron neutron capture therapy. Radiat Prot Dosimetry 161:269–273. https://doi.org/10.1093/rpd/nct365
Article Google Scholar
Laird JH, Lok BH, Ma J et al (2018) Talazoparib is a potent radiosensitizer in small cell lung cancer cell lines and xenografts. Clin Cancer Res 24:5143–5152. https://doi.org/10.1158/1078-0432.CCR-18-0401
Article Google Scholar
Laurie SA, Jeyabalan N, Nicholas G et al (2006) Association between anemia arising during therapy and outcomes of chemoradiation for limited small-cell lung cancer. J Thorac Oncol 1:146–151. https://doi.org/10.1016/s1556-0864(15)31530-6
Article Google Scholar
Lee DJ, Cosmatos D, Marcial VA et al (1995) Results of an RTOG phase III trial (RTOG 85-27) comparing radiotherapy plus etanidazole with radiotherapy alone for locally advanced head and neck carcinomas. Int J Radiat Oncol Biol Phys 32:567–576. https://doi.org/10.1016/0360-3016(95)00150-W
Article Google Scholar
Lee S, Lim M-J, Kim M-H et al (2012) An effective strategy for increasing the radiosensitivity of human lung cancer cells by blocking Nrf2-dependent antioxidant responses. Free Radic Biol Med 53:807–816. https://doi.org/10.1016/j.freeradbiomed.2012.05.038
Article Google Scholar
Lee S-l-o, Son AR, Ahn J, Song JY (2014) Niclosamide enhances ROS-mediated cell death through c-Jun activation. Biomed Pharmacother 68:619–624. https://doi.org/10.1016/j.biopha.2014.03.018
Article Google Scholar
Lee DE, Alhallak K, Jenkins SV et al (2018) A radiosensitizing inhibitor of HIF-1 alters the optical redox state of human lung cancer cells in vitro. Sci Rep 8:1–10. https://doi.org/10.1038/s41598-018-27262-y
Article Google Scholar
Lei Y, Li HX, Sen JW et al (2013) The radiosensitizing effect of Paeonol on lung adenocarcinoma by augmentation of radiation-induced apoptosis and inhibition of the PI3K/Akt pathway. Int J Radiat Biol 89:1079–1086. https://doi.org/10.3109/09553002.2013.825058
Article Google Scholar
Leyland-Jones B (2003) Reflection and reaction breast cancer trial with erythropoietin terminated unexpectedly. Lancet 4:459–460
Article Google Scholar
Li N, Tian G-W, Tang L-R, Li G (2019) hMOF reduction enhances radiosensitivity through the homologous recombination pathway in non-small-cell lung cancer. Onco Targets Ther 12:3065–3075. https://doi.org/10.2147/ott.s192568
Article Google Scholar
Lin SH, Zhang J, Giri U et al (2014) A high content clonogenic survival drug screen identifies MEK inhibitors as potent radiation sensitizers for KRAS mutant non-small-cell lung cancer. J Thorac Oncol 9:965–973. https://doi.org/10.1097/JTO.0000000000000199
Article Google Scholar
Liu X, Chen H, Xu X et al (2018) Insulin-like growth factor-1 receptor knockdown enhances radiosensitivity via the HIF-1α pathway and attenuates ATM/H2AX/53BP1 DNA repair activation in human lung squamous carcinoma cells. Oncol Lett 16:1332–1340. https://doi.org/10.3892/ol.2018.8705
Article Google Scholar
Loriot Y, Mordant P, Dugue D et al (2014) Radiosensitization by a novel Bcl-2 and Bcl-XL inhibitor S44563 in small-cell lung cancer. Cell Death Dis 5:1–13. https://doi.org/10.1038/cddis.2014.365
Article Google Scholar
Luo H, Wang L, Schulte BA et al (2013) Resveratrol enhances ionizing radiation-induced premature senescence in lung cancer cells. Int J Oncol 43:1999–2006. https://doi.org/10.3892/ijo.2013.2141
Article Google Scholar
MacRae R, Shyr Y, Johnson D, Choy H (2002) Declining hemoglobin during chemoradiotherapy for locally advanced non-small cell lung cancer is significant. Radiother Oncol 64:37–40. https://doi.org/10.1016/S0167-8140(02)00151-2
Article Google Scholar
Marks PA, Richon VM, Rifkind RA (2000) Histone deacetylase inhibitors: inducers of differentiation or apoptosis of transformed cells. J Natl Cancer Inst 92:1210–1216. https://doi.org/10.1093/jnci/92.15.1210
Article Google Scholar
Matschke J, Wiebeck E, Hurst S et al (2016) Role of SGK1 for fatty acid uptake, cell survival and radioresistance of NCI-H460 lung cancer cells exposed to acute or chronic cycling severe hypoxia. Radiat Oncol 11:1–12. https://doi.org/10.1186/s13014-016-0647-1
Article Google Scholar
McGowan DR, Skwarski M, Bradley KM et al (2019) Buparlisib with thoracic radiotherapy and its effect on tumour hypoxia: a phase I study in patients with advanced non-small cell lung carcinoma. Eur J Cancer 113:87–95. https://doi.org/10.1016/j.ejca.2019.03.015
Article Google Scholar
McLaughlin KA, Nemeth Z, Bradley CA et al (2016) FLIP: a targetable mediator of resistance to radiation in non-small cell lung cancer. Mol Cancer Ther 15:2432–2441. https://doi.org/10.1158/1535-7163.MCT-16-0211
Article Google Scholar
Ménissier De Murcia J, Niedergang C, Trucco C et al (1997) Requirement of poly(ADP-ribose) polymerase in recovery from DNA damage in mice and in cells. Proc Natl Acad Sci U S A 94:7303–7307. https://doi.org/10.1073/pnas.94.14.7303
Article Google Scholar
Moretti L, Li B, Kim KW et al (2010) AT-101, a Pan-Bcl-2 inhibitor, leads to radiosensitization of non-small cell lung cancer. J Thorac Oncol 5:680–687. https://doi.org/10.1097/JTO.0b013e3181d6e08e
Article Google Scholar
Motea EA, Huang X, Singh N et al (2020) NQO1-dependent, tumor-selective radiosensitization of non-small cell lung cancers. Clin Cancer Res 25:2601–2609. https://doi.org/10.1158/1078-0432.CCR-18-2560
Article Google Scholar
Mutter R, Lu B, Carbone DP et al (2009) A phase II study of celecoxib in combination with paclitaxel, carboplatin, and radiotherapy for patients with inoperable stage IIIA/B non-small cell lung cancer. Clin Cancer Res 15:2158–2165. https://doi.org/10.1158/1078-0432.CCR-08-0629
Article Google Scholar
Nolte EM, Joubert AM, Lakier R et al (2018) Exposure of breast and lung cancer cells to a novel estrone analog prior to radiation enhances Bcl-2-mediated cell death. Int J Mol Sci 19:2887. https://doi.org/10.3390/ijms19102887
Article Google Scholar
Ohsaki Y, Tanno S, Fujita Y et al (2000) Epidermal growth factor receptor expression correlates with poor prognosis in non-small cell lung cancer patients with p53 overexpression. Oncol Rep 7:603–607. https://doi.org/10.3892/or.7.3.603
Article Google Scholar
Oike T, Komachi M, Ogiwara H et al (2014) C646, a selective small molecule inhibitor of histone acetyltransferase p300, radiosensitizes lung cancer cells by enhancing mitotic catastrophe. Radiother Oncol 111:222–227. https://doi.org/10.1016/j.radonc.2014.03.015
Article Google Scholar
Park JK, Chung YM, Kim BG et al (2004) N′-(phenyl-2-yl-methylene)-hydrazine carbodithioic acid methyl ester enhances radiation-induced cell death by targeting Bcl-2 against human lung carcinoma cells. Mol Cancer Ther 3:403–407
Article Google Scholar
Park SY, Kim YM, Pyo H (2010) Gefitinib radiosensitizes non-small cell lung cancer cells through inhibition of ataxia telangiectasia mutated. Mol Cancer 9:1–12. https://doi.org/10.1186/1476-4598-9-222
Article Google Scholar
Parsels LA, Karnak D, Parsels JD et al (2018) PARP1 trapping and DNA replication stress enhance radiosensitization with combined WEE1 and PARP inhibitors. Mol Cancer Res 16:222–232. https://doi.org/10.1158/1541-7786.MCR-17-0455
Article Google Scholar
Reymen BJT, van Gisbergen MW, Even AJG et al (2020) Nitroglycerin as a radiosensitizer in non-small cell lung cancer: results of a prospective imaging-based phase II trial. Clin Transl Radiat Oncol 21:49–55. https://doi.org/10.1016/j.ctro.2019.12.002
Article Google Scholar
Riches LC, Trinidad AG, Hughes G et al (2020) Pharmacology of the ATM inhibitor AZD0156: potentiation of irradiation and olaparib responses preclinically. Mol Cancer Ther 19:13–25. https://doi.org/10.1158/1535-7163.MCT-18-1394
Article Google Scholar
Rischin D, Peters LJ, O’Sullivan B et al (2010) Tirapazamine, cisplatin, and radiation versus cisplatin and radiation for advanced squamous cell carcinoma of the head and neck (TROG 02.02, headstart): a phase III trial of the Trans-Tasman Radiation Oncology Group. J Clin Oncol 28:2989–2995. https://doi.org/10.1200/JCO.2009.27.4449
Article Google Scholar
Rivera S, Leteur C, Mégnin F et al (2017) Time dependent modulation of tumor radiosensitivity by a pan HDAC inhibitor: abexinostat. Oncotarget 8:56210–56227. https://doi.org/10.18632/oncotarget.14813
Article Google Scholar
Robnett TJ, Machtay M, Hahn SM et al (2002) Pathological response to preoperative chemoradiation worsens with anemia in non-small cell lung cancer patients. Cancer J 8:263–267. https://doi.org/10.1097/00130404-200205000-00010
Article Google Scholar
Rubin P, Hanley J, Keys HM et al (1979) Carbogen breathing during radiation therapy—the radiation therapy oncology group study. Int J Radiat Oncol Biol Phys 5:1963–1970. https://doi.org/10.1016/0360-3016(79)90946-5
Article Google Scholar
Rudin CM, Salgia R, Wang X et al (2008) Randomized phase II study of carboplatin and etoposide with or without the bcl-2 antisense oligonucleotide oblimersen for extensive-stage small-cell lung cancer: CALGB 30103. J Clin Oncol 26:870–876. https://doi.org/10.1200/JCO.2007.14.3461
Article Google Scholar
Saki M, Makino H, Javvadi P et al (2017) EGFR mutations compromise hypoxia-associated radiation resistance through impaired replication fork-associated DNA damage repair. Mol Cancer Res 15:1503–1516. https://doi.org/10.1158/1541-7786.MCR-17-0136
Article Google Scholar
Schilling D, Bayer C, Li W et al (2012) Radiosensitization of normoxic and hypoxic H1339 lung tumor cells by heat shock protein 90 inhibition is independent of hypoxia inducible factor-1α. PLoS One 7:1–11. https://doi.org/10.1371/journal.pone.0031110
Article Google Scholar
Scott C, Suh J, Stea B et al (2007) Improved survival, quality of life, and quality-adjusted survival in breast cancer patients treated with efaproxiral (Efaproxyn) plus whole-brain radiation therapy for brain metastases. Am J Clin Oncol 30:580–587. https://doi.org/10.1097/COC.0b013e3180653c0d
Article Google Scholar
Senra JM, Telfer BA, Cherry KE et al (2011) Inhibition of PARP-1 by olaparib (AZD2281) increases the radiosensitivity of a lung tumor xenograft. Mol Cancer Ther 10:1949–1958. https://doi.org/10.1158/1535-7163.MCT-11-0278
Article Google Scholar
Seo SK, Jin HO, Woo SH et al (2011) Histone deacetylase inhibitors sensitize human non-small cell lung cancer cells to ionizing radiation through acetyl p53-mediated c-myc down-regulation. J Thorac Oncol 6:1313–1319. https://doi.org/10.1097/JTO.0b013e318220caff
Article Google Scholar
Shannon AM, Telfer BA, Smith PD et al (2009) The mitogen-activated protein/extracellular signal-regulated kinase kinase 1/2 inhibitor AZD6244 (ARRY-142886) enhances the radiation responsiveness of lung and colorectal tumor xenografts. Clin Cancer Res 15:6619–6629. https://doi.org/10.1158/1078-0432.CCR-08-2958
Article Google Scholar
Storozhuk Y, Hopmans SN, Sanli T et al (2013) Metformin inhibits growth and enhances radiation response of non-small cell lung cancer (NSCLC) through ATM and AMPK. Br J Cancer 108:2021–2032. https://doi.org/10.1038/bjc.2013.187
Article Google Scholar
Suh JH, Stea B, Nabid A et al (2006) Phase III study of efaproxiral as an adjunct to whole-brain radiation therapy for brain metastases. J Clin Oncol 24:106–114. https://doi.org/10.1200/JCO.2004.00.1768
Article Google Scholar
Sun KK, Zhong N, Yang Y et al (2013) Enhanced radiosensitivity of NSCLC cells by transducer of erbB2.1 (TOB1) through modulation of the MAPK/ERK pathway. Oncol Rep 29:2385–2391. https://doi.org/10.3892/or.2013.2403
Article Google Scholar
Sun J, Liu N-B, Zhuang H-Q et al (2017) Celecoxib-erlotinib combination treatment enhances radiosensitivity in A549 human lung cancer cell. Cancer Biomark 19:45–50. https://doi.org/10.3233/CBM-160323
Article Google Scholar
Sun Y, Dai H, Chen S et al (2018) Disruption of chromosomal architecture of cox2 locus sensitizes lung cancer cells to radiotherapy. Mol Ther 26:2456–2465. https://doi.org/10.1016/j.ymthe.2018.08.002
Article Google Scholar
Suzuki M (2020) Boron neutron capture therapy (BNCT): a unique role in radiotherapy with a view to entering the accelerator-based BNCT era. Int J Clin Oncol 25:43–50. https://doi.org/10.1007/s10147-019-01480-4
Article Google Scholar
Trivillin VA, Serrano A, Garabalino MA et al (2019) Translational boron neutron capture therapy (BNCT) studies for the treatment of tumors in lung. Int J Radiat Biol 95:646–654. https://doi.org/10.1080/09553002.2019.1564080
Article Google Scholar
Vansteenkiste J, Pirker R, Massuti B et al (2002) Double-blind, placebo-controlled, randomized phase III trial of darbepoetin alfa in lung cancer patients receiving chemotherapy. J Natl Cancer Inst 94:1211–1220. https://doi.org/10.1093/jnci/94.16.1211
Article Google Scholar
Walls GM, Oughton JB, Chalmers AJ et al (2020) CONCORDE: a phase I platform study of novel agents in combination with conventional radiotherapy in non-small-cell lung cancer. Clin Transl Radiat Oncol 25:61–66. https://doi.org/10.1016/j.ctro.2020.09.006
Article Google Scholar
Wang L, Raju U, Milas L et al (2011) Huachansu, containing cardiac glycosides, enhances radiosensitivity of human lung cancer cells. Anticancer Res 31:2141–2148
Google Scholar
Wang L, Mason KA, Ang KK et al (2012) MK-4827, a PARP-1/-2 inhibitor, strongly enhances response of human lung and breast cancer xenografts to radiation. Invest New Drugs 30:2113–2120. https://doi.org/10.1007/s10637-011-9770-x
Article Google Scholar
Wang G, Xiao L, Wang F et al (2019) Hypoxia inducible factor-1α/B-cell lymphoma 2 signaling impacts radiosensitivity of H1299 non-small cell lung cancer cells in a normoxic environment. Radiat Environ Biophys 58:439–448. https://doi.org/10.1007/s00411-019-00802-4
Article Google Scholar
Watson ER, Halnan KE, Dische S et al (1978) Hyperbaric oxygen and radiotherapy: a Medical Research Council trial in carcinoma of the cervix. Br J Radiol 51:879–887. https://doi.org/10.1259/0007-1285-51-611-879
Article Google Scholar
Wéra AC, Lobbens A, Stoyanov M et al (2019) Radiation-induced synthetic lethality: combination of poly(ADP-ribose) polymerase and RAD51 inhibitors to sensitize cells to proton irradiation. Cell Cycle 18:1770–1783. https://doi.org/10.1080/15384101.2019.1632640
Article Google Scholar
Wilson WR, Denny WA, Pullen SM et al (1996) Tertiary amine N-oxides as bioreductive drugs: DACA N-oxide, nitracrine N-oxide and AQ4N. Br J Cancer 27:S43–S47
Google Scholar
Xiang M, Chen Z, Yang D et al (2017) Niclosamide enhances the antitumor effects of radiation by inhibiting the hypoxia-inducible factor-1α/vascular endothelial growth factor signaling pathway in human lung cancer cells. Oncol Lett 14:1933–1938. https://doi.org/10.3892/ol.2017.6372
Article Google Scholar
Xu Z, Zuo Y, Wang J et al (2015) Overexpression of the regulator of G-protein signaling 5 reduces the survival rate and enhances the radiation response of human lung cancer cells. Oncol Rep 33:2899–2907. https://doi.org/10.3892/or.2015.3917
Article Google Scholar
Yamamoto M, Izumi Y, Horinouchi H et al (2009) Systemic administration of hemoglobin vesicle elevates tumor tissue oxygen tension and modifies tumor response to irradiation. J Surg Res 151:48–54. https://doi.org/10.1016/j.jss.2007.12.770
Article Google Scholar
Yang HJ, Kim N, Seong KM et al (2013) Investigation of radiation-induced transcriptome profile of radioresistant non-small cell lung cancer A549 cells using RNA-seq. PLoS One 8:e59319. https://doi.org/10.1371/journal.pone.0059319
Article Google Scholar
Yu H, Tang X, Shu D et al (2017) Influence of neutron sources and 10B concentration on boron neutron capture therapy for shallow and deeper non-small cell lung cancer. Health Phys 112:258–265. https://doi.org/10.1097/HP.0000000000000601
Article Google Scholar
Zhang Y, Adachi M, Zhao X et al (2004) Histone deacetylase inhibitors FK228, N-(2-aminophenyl)-4-[N-(pyridin-3-yl-methoxycarbonyl)amino-methyl]benzamide and m-carboxycinnamic acid bis-hydroxamide augment radiation-induced cell death in gastrointestinal adenocarcinoma cells. Int J Cancer 110:301–308. https://doi.org/10.1002/ijc.20117
Article Google Scholar
Zhang F, Zhang T, Teng ZH et al (2009) Sensitization to γ-irradiation-induced cell cycle arrest and apoptosis by the histone deacetylase inhibitor trichostatin A in non-small cell lung cancer (NSCLC) cells. Cancer Biol Ther 8:823–831. https://doi.org/10.4161/cbt.8.9.8143
Article Google Scholar
Zhang S, Fu Y, Wang D, Wang J (2018) Icotinib enhances lung cancer cell radiosensitivity in vitro and in vivo by inhibiting MAPK/ERK and AKT activation. Clin Exp Pharmacol Physiol 45:969–977. https://doi.org/10.1111/1440-1681.12966
Article Google Scholar
Zhang F, Fan B, Mao L (2019a) Radiosensitizing effects of Cyclocarya paliurus polysaccharide on hypoxic A549 and H520 human non-small cell lung carcinoma cells. Int J Mol Med 44:1233–1242. https://doi.org/10.3892/ijmm.2019.4289
Article Google Scholar
Zhang P, He D, Song E et al (2019b) Celecoxib enhances the sensitivity of nonsmall-cell lung cancer cells to radiation-induced apoptosis through downregulation of the Akt/mTOR signaling pathway and COX-2 expression. PLoS One 14:1–15. https://doi.org/10.1371/journal.pone.0223760
Article Google Scholar
Zhang N, Song Y, Xu Y et al (2020) MED13L integrates mediator-regulated epigenetic control into lung cancer radiosensitivity. Theranostics 10:9378–9394. https://doi.org/10.7150/thno.48247
Article Google Scholar

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Mansi K. Aparnathi and Sami Ul Haq contributed equally with all other contributors.

Authors and Affiliations

Radiation Medicine Program, Princess Margaret Cancer Centre/University Health Network, Toronto, ON, Canada
Mansi K. Aparnathi & Benjamin H. Lok
Institute of Medical Science, University of Toronto, Toronto, ON, Canada
Sami Ul Haq & Benjamin H. Lok
Department of Radiation Oncology, Southlake Regional Health Centre, Newmarket, ON, Canada
Zishan Allibhai
Department of Radiation Oncology, University of Toronto, Toronto, ON, Canada
Zishan Allibhai, Benjamin H. Lok & Anthony M. Brade
Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada
Benjamin H. Lok
Department of Radiation Oncology, Peel Regional Cancer Centre, Credit Valley Hospital, Trillium Health Partners, Mississauga, ON, Canada
Anthony M. Brade

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Mansi K. Aparnathi
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Sami Ul Haq
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Zishan Allibhai
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Benjamin H. Lok
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Anthony M. Brade
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School of Medicine, University of Kragujevac, Kragujevac, Serbia
Branislav Jeremić

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Aparnathi, M.K., Haq, S.U., Allibhai, Z., Lok, B.H., Brade, A.M. (2022). Radiation Sensitizers. In: Jeremić, B. (eds) Advances in Radiation Oncology in Lung Cancer. Medical Radiology(). Springer, Cham. https://doi.org/10.1007/174_2022_319

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DOI: https://doi.org/10.1007/174_2022_319
Published: 20 December 2022
Publisher Name: Springer, Cham
Print ISBN: 978-3-031-34846-4
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