Growth hormone and radiation therapy: friend, foe, or both?

in Endocrine-Related Cancer
Authors:
Verónica A Bahamondes Lorca Edison Biotechnology Institute, Ohio University, Athens, Ohio, USA
Departamento de Tecnología Médica, Facultad de Medicina, Universidad de Chile, Santiago, Chile

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Shiyong Wu Edison Biotechnology Institute, Ohio University, Athens, Ohio, USA
Department of Chemistry and Biochemistry, Ohio University, Athens, Ohio, USA

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Correspondence should be addressed to S Wu: wus1@ohio.edu

This paper is part of a themed collection on the role of Growth Hormone in Endocrine Cancers. The Guest Editor for this collection was John Kopchick, Ohio University, USA.

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Radiotherapy is one of the major options currently for cancer treatment. Radiotherapy causes cellular damage inducing cell death, which is expected to be selective for tumor cells. However, side effects that alter the surrounding normal tissue are often hard to be avoided. When radiation involves the hypothalamic–pituitary axis, growth hormone deficiency (GHD) is frequently induced, causing developmental and metabolic-related diseases in childhood cancer survivors. Growth hormone (GH) replacement therapy has been used for these patients and has been shown to be safe in general. However, there are some debating for its long-term safety due to the known roles of GH in inducing cell growth, which could be related to cancer recurrence. In addition, studies have shown that GH is involved in the development of resistance to chemotherapy and radiotherapy through various mechanisms. In this review, we will first discuss the effects of GHD induced after radiotherapy and the safety of the GH replacement treatment. Then, we will discuss the role of the GH–IGF-1 axis in radioresistance via a mechanism of improving DNA repair.

 

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  • Aleksic T, Verrill C, Bryant RJ, Han C, Worrall AR, Brureau L, Larré S, Higgins GS, Fazal F, Sabbagh A, et al.2017 IGF-1R associates with adverse outcomes after radical radiotherapy for prostate cancer. British Journal of Cancer 117 16001606. (https://doi.org/10.1038/bjc.2017.337)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Alves-Fernandes DK & & Jasiulionis MG 2019 The role of SIRT1 on DNA damage response and epigenetic alterations in cancer. International Journal of Molecular Sciences 20. (https://doi.org/10.3390/ijms20133153)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Babel L, Grunewald M, Lehn R, Langhans M & & Meckel T 2017 Direct evidence for cell adhesion-mediated radioresistance (CAM-RR) on the level of individual integrin β1 clusters. Scientific Reports 7 3393. (https://doi.org/10.1038/s41598-017-03414-4)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Barker HE, Paget JT, Khan AA & & Harrington KJ 2015 The tumour microenvironment after radiotherapy: mechanisms of resistance and recurrence. Nature Reviews. Cancer 15 409425. (https://doi.org/10.1038/nrc3958)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Baskar R, Lee KA, Yeo R & & Yeoh KW 2012 Cancer and radiation therapy: current advances and future directions. International Journal of Medical Sciences 9 193199. (https://doi.org/10.7150/ijms.3635)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Basu R & & Kopchick JJ 2019 The effects of growth hormone on therapy resistance in cancer. Cancer Drug Resistance 2 827846. (https://doi.org/10.20517/cdr.2019.27)

  • Basu R, Qian Y, Mathes S, Terry J, Arnett N, Riddell T, Stevens A, Funk K, Bell S, Bokal Z, et al.2022 Growth hormone receptor antagonism downregulates ATP-binding cassette transporters contributing to improved drug efficacy against melanoma and hepatocarcinoma in vivo. Frontiers in Oncology 12 936145. (https://doi.org/10.3389/fonc.2022.936145)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Beckers D, Thomas M, Jamart J, Francois I, Maes M, Lebrethon MC, De Waele K, Tenoutasse S & & De Schepper J 2010 Adult final height after GH therapy for irradiation-induced GH deficiency in childhood survivors of brain tumors: the Belgian experience. European Journal of Endocrinology 162 483490. (https://doi.org/10.1530/EJE-09-0690)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Biau J, Chautard E, Verrelle P & & Dutreix M 2019 Altering DNA repair to improve radiation therapy: specific and multiple pathway targeting. Frontiers in Oncology 9 1009. (https://doi.org/10.3389/fonc.2019.01009)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Bidlingmaier M & & Strasburger CJ 2009 Growth hormone. Handbook of Experimental Pharmacology 195 187200. (https://doi.org/10.1007/978-3-540-79088-4_8)

  • Boguszewski CL & & Ayuk J 2016 Management of endocrine disease: acromegaly and cancer: an old debate revisited. European Journal of Endocrinology 175 R147R156. (https://doi.org/10.1530/EJE-16-0178)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Boguszewski MCS, Cardoso-Demartini AA, Boguszewski CL, Chemaitilly W, Higham CE, Johannsson G & & Yuen KCJ 2021 Safety of growth hormone (GH) treatment in GH deficient children and adults treated for cancer and non-malignant intracranial tumors-a review of research and clinical practice. Pituitary 24 810827. (https://doi.org/10.1007/s11102-021-01173-0)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Boguszewski MCS, Boguszewski CL, Chemaitilly W, Cohen LE, Gebauer J, Higham C, Hoffman AR, Polak M, Yuen KCJ, Alos N, et al.2022 Safety of growth hormone replacement in survivors of cancer and intracranial and pituitary tumours: a consensus statement. European Journal of Endocrinology 186 P35P52. (https://doi.org/10.1530/EJE-21-1186)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Bolfi F, Neves AF, Boguszewski CL & & Nunes-Nogueira VS 2018 Mortality in acromegaly decreased in the last decade: a systematic review and meta-analysis. European Journal of Endocrinology 179 5971. (https://doi.org/10.1530/EJE-18-0255)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Bougen NM, Yang T, Chen H, Lobie PE & & Perry JK 2011 Autocrine human growth hormone reduces mammary and endometrial carcinoma cell sensitivity to Mitomycin C. Oncology Reports 26 487493. (https://doi.org/10.3892/or.2011.1305)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Bougen NM, Steiner M, Pertziger M, Banerjee A, Brunet-Dunand SE, Zhu T, Lobie PE & & Perry JK 2012 Autocrine human GH promotes radioresistance in mammary and endometrial carcinoma cells. Endocrine-Related Cancer 19 625644. (https://doi.org/10.1530/ERC-12-0042)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Brauner R, Czernichow P & & Rappaport R 1986 Greater susceptibility to hypothalamopituitary irradiation in younger children with acute lymphoblastic leukemia. Journal of Pediatrics 108 332. (https://doi.org/10.1016/s0022-3476(8681027-7)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Brauner R, Malandry F, Rappaport R, Zucker JM, Kalifa C, Pierre-Kahn A, Bataini P & & Dufier JL 1990 Growth and endocrine disorders in optic glioma. European Journal of Pediatrics 149 825828. (https://doi.org/10.1007/BF02072067)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Brignardello E, Felicetti F, Castiglione A, Fortunati N, Matarazzo P, Biasin E, Sacerdote C, Ricardi U, Fagioli F, Corrias A, et al.2015 GH replacement therapy and second neoplasms in adult survivors of childhood cancer: a retrospective study from a single institution. Journal of Endocrinological Investigation 38 171176. (https://doi.org/10.1007/s40618-014-0179-1)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Brook I 2020 Late side effects of radiation treatment for head and neck cancer. Radiation Oncology Journal 38 8492. (https://doi.org/10.3857/roj.2020.00213)

  • Bülow B, Hagmar L, Mikoczy Z, Nordström CH & & Erfurth EM 1997 Increased cerebrovascular mortality in patients with hypopituitarism. Clinical Endocrinology 46 7581. (https://doi.org/10.1046/j.1365-2265.1997.d01-1749.x)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Bülow B, Link K, Ahrén B, Nilsson AS & & Erfurth EM 2004 Survivors of childhood acute lymphoblastic leukaemia, with radiation-induced GH deficiency, exhibit hyperleptinaemia and impaired insulin sensitivity, unaffected by 12 months of GH treatment. Clinical Endocrinology 61 683691. (https://doi.org/10.1111/j.1365-2265.2004.02149.x)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Calabrese CR, Almassy R, Barton S, Batey MA, Calvert AH, Canan-Koch S, Durkacz BW, Hostomsky Z, Kumpf RA, Kyle S, et al.2004 Anticancer chemosensitization and radiosensitization by the novel poly(ADP-ribose) polymerase-1 inhibitor AG14361. Journal of the National Cancer Institute 96 5667. (https://doi.org/10.1093/jnci/djh005)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Castinetti F, Morange I, Dufour H, Regis J & & Brue T 2009 Radiotherapy and radiosurgery in acromegaly. Pituitary 12 310. (https://doi.org/10.1007/s11102-007-0078-y)

  • Caz V, Elvira M, Tabernero M, Grande AG, Lopez-Plaza B, de Miguel E, Largo C & & Santamaria M 2015 Growth hormone protects the intestine preserving radiotherapy efficacy on tumors: a short-term study. PLoS One 10 e0144537. (https://doi.org/10.1371/journal.pone.0144537)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Chadderton RD, West CG, Schuller S, Quirke DC, Gattamaneni R & & Taylor R 1995 Radiotherapy in the treatment of low-grade astrocytomas. II. The physical and cognitive sequelae. Child’s Nervous System 11 443448. (https://doi.org/10.1007/BF00334961)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Chan DW, Chen BP, Prithivirajsingh S, Kurimasa A, Story MD, Qin J & & Chen DJ 2002 Autophosphorylation of the DNA-dependent protein kinase catalytic subunit is required for rejoining of DNA double-strand breaks. Genes and Development 16 23332338. (https://doi.org/10.1101/gad.1015202)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Chen HHW & & Kuo MT 2017 Improving radiotherapy in cancer treatment: promises and challenges. Oncotarget 8 6274262758. (https://doi.org/10.18632/oncotarget.18409)

  • Cheng Y, Li W, Gui R, Wang C, Song J, Wang Z, Wang X, Shen Y, Wang Z & & Hao L 2021 Dual characters of GH-IGF1 signaling pathways in radiotherapy and post-radiotherapy repair of cancers. Frontiers in Cell and Developmental Biology 9 671247. (https://doi.org/10.3389/fcell.2021.671247)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Chesnokova V, Zhou C, Ben-Shlomo A, Zonis S, Tani Y, Ren SG & & Melmed S 2013 Growth hormone is a cellular senescence target in pituitary and nonpituitary cells. PNAS 110 E3331E3339. (https://doi.org/10.1073/pnas.1310589110)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Chesnokova V, Zonis S, Zhou C, Recouvreux MV, Ben-Shlomo A, Araki T, Barrett R, Workman M, Wawrowsky K, Ljubimov VA, et al.2016 Growth hormone is permissive for neoplastic colon growth. PNAS 113 E3250E3259. (https://doi.org/10.1073/pnas.1600561113)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Chesnokova V, Zonis S, Barrett R, Kameda H, Wawrowsky K, Ben-Shlomo A, Yamamoto M, Gleeson J, Bresee C, Gorbunova V, et al.2019 Excess growth hormone suppresses DNA damage repair in epithelial cells. JCI Insight 4 e125762. (https://doi.org/10.1172/jci.insight.125762)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Chitnis MM, Lodhia KA, Aleksic T, Gao S, Protheroe AS & & Macaulay VM 2014 IGF-1R inhibition enhances radiosensitivity and delays double-strand break repair by both non-homologous end-joining and homologous recombination. Oncogene 33 52625273. (https://doi.org/10.1038/onc.2013.460)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Collett-Solberg PF, Ambler G, Backeljauw PF, Bidlingmaier M, Biller BMK, Boguszewski MCS, Cheung PT, Choong CSY, Cohen LE, Cohen P, et al.2019 Diagnosis, genetics, and therapy of short stature in children: a Growth Hormone Research Society international perspective. Hormone Research in Paediatrics 92 114. (https://doi.org/10.1159/000502231)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Cosaceanu D, Budiu RA, Carapancea M, Castro J, Lewensohn R & & Dricu A 2007 Ionizing radiation activates IGF-1R triggering a cytoprotective signaling by interfering with Ku-DNA binding and by modulating Ku86 expression via a p38 kinase-dependent mechanism. Oncogene 26 24232434. (https://doi.org/10.1038/sj.onc.1210037)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Couto-Silva AC, Trivin C, Esperou H, Michon J, Baruchel A, Lemaire P & & Brauner R 2006 Final height and gonad function after total body irradiation during childhood. Bone Marrow Transplantation 38 427432. (https://doi.org/10.1038/sj.bmt.1705455)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Danilowicz K & & Sosa S 2023 Acromegaly and cancer: an update. Archives of Medical Research 54 102914. (https://doi.org/10.1016/j.arcmed.2023.102914)

  • Darragh LB, Oweida AJ & & Karam SD 2018 Overcoming resistance to combination radiation-immunotherapy: a focus on contributing pathways within the tumor microenvironment. Frontiers in Immunology 9 3154. (https://doi.org/10.3389/fimmu.2018.03154)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Darzy KH & & Shalet SM 2006 Pathophysiology of radiation-induced growth hormone deficiency: efficacy and safety of GH replacement. Growth Hormone and IGF Research 16(Supplement A) S30S40. (https://doi.org/10.1016/j.ghir.2006.03.002)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Díez JJ, Sangiao-Alvarellos S & & Cordido F 2018 Treatment with growth hormone for adults with growth hormone deficiency syndrome: benefits and risks. International Journal of Molecular Sciences 19 893. (https://doi.org/10.3390/ijms19030893)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Divisova J, Kuiatse I, Lazard Z, Weiss H, Vreeland F, Hadsell DL, Schiff R, Osborne CK & & Lee AV 2006 The growth hormone receptor antagonist pegvisomant blocks both mammary gland development and MCF-7 breast cancer xenograft growth. Breast Cancer Research and Treatment 98 315327. (https://doi.org/10.1007/s10549-006-9168-1)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Eaton BR, Esiashvili N, Kim S, Patterson B, Weyman EA, Thornton LT, Mazewski C, MacDonald TJ, Ebb D, MacDonald SM, et al.2016 Endocrine outcomes with proton and photon radiotherapy for standard risk medulloblastoma. Neuro-Oncology 18 881887. (https://doi.org/10.1093/neuonc/nov302)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Eke I, Dickreuter E & & Cordes N 2012 Enhanced radiosensitivity of head and neck squamous cell carcinoma cells by β1 integrin inhibition. Radiotherapy and Oncology 104 235242. (https://doi.org/10.1016/j.radonc.2012.05.009)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Ergun-Longmire B, Mertens AC, Mitby P, Qin J, Heller G, Shi W, Yasui Y, Robison LL & & Sklar CA 2006 Growth hormone treatment and risk of second neoplasms in the childhood cancer survivor. Journal of Clinical Endocrinology and Metabolism 91 34943498. (https://doi.org/10.1210/jc.2006-0656)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Esposito D, Ragnarsson O, Johannsson G & & Olsson DS 2021 Incidence of benign and malignant tumors in patients with acromegaly is increased: a nationwide population-based study. Journal of Clinical Endocrinology and Metabolism 106 34873496. (https://doi.org/10.1210/clinem/dgab560)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Evans A, Jamieson SM, Liu DX, Wilson WR & & Perry JK 2016 Growth hormone receptor antagonism suppresses tumour regrowth after radiotherapy in an endometrial cancer xenograft model. Cancer Letters 379 117123. (https://doi.org/10.1016/j.canlet.2016.05.031)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Galeaz C, Totis C & & Bisio A 2021 Radiation resistance: a matter of transcription factors. Frontiers in Oncology 11 662840. (https://doi.org/10.3389/fonc.2021.662840)

  • Gan Y, Buckels A, Liu Y, Zhang Y, Paterson AJ, Jiang J, Zinn KR & & Frank SJ 2014 Human GH receptor-IGF-1 receptor interaction: implications for GH signaling. Molecular Endocrinology 28 18411854. (https://doi.org/10.1210/me.2014-1174)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Gheorghiu ML 2017 Updates in outcomes of stereotactic radiation therapy in acromegaly. Pituitary 20 154168. (https://doi.org/10.1007/s11102-016-0783-5)

  • Gheorghiu ML & & Fleseriu M 2017 Stereotactic radiation therapy in pituitary adenomas, is it better than conventional radiation therapy? Acta Endocrinology 13 476490. (https://doi.org/10.4183/aeb.2017.476)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Giuranno L, Ient J, De Ruysscher D & & Vooijs MA 2019 Radiation-induced lung injury (RILI). Frontiers in Oncology 9 877. (https://doi.org/10.3389/fonc.2019.00877)

  • Gleeson HK, Darzy K & & Shalet SM 2002 Late endocrine, metabolic and skeletal sequelae following treatment of childhood cancer. Best Practice and Research. Clinical Endocrinology and Metabolism 16 335348. (https://doi.org/10.1053/beem.2002.0201)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Gleeson HK, Stoeter R, Ogilvy-Stuart AL, Gattamaneni HR, Brennan BM & & Shalet SM 2003 Improvements in final height over 25 years in growth hormone (GH)-deficient childhood survivors of brain tumors receiving GH replacement. Journal of Clinical Endocrinology and Metabolism 88 36823689. (https://doi.org/10.1210/jc.2003-030366)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Gómez-de-Segura IA, Prieto I, Grande AG, García P, Guerra A, Mendez J & & De Miguel E 1998 Growth hormone reduces mortality and bacterial translocation in irradiated rats. Acta Oncologica 37 179185. (https://doi.org/10.1080/028418698429748)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Greenberger BA, Pulsifer MB, Ebb DH, MacDonald SM, Jones RM, Butler WE, Huang MS, Marcus KJ, Oberg JA, Tarbell NJ, et al.2014 Clinical outcomes and late endocrine, neurocognitive, and visual profiles of proton radiation for pediatric low-grade gliomas. International Journal of Radiation Oncology, Biology, Physics 89 10601068. (https://doi.org/10.1016/j.ijrobp.2014.04.053)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Hakuno F & & Takahashi SI 2018 40 YEARS OF IGF1: IGF1 receptor signaling pathways. Journal of Molecular Endocrinology 61 T69T86. (https://doi.org/10.1530/JME-17-0311)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • He M, Deng X, Wang X, Wan Y, Huang J, Zhang Z & & Niu W 2022 Association between recombinant growth hormone therapy and all-cause mortality and cancer risk in childhood: systematic review and meta-analysis. Frontiers in Pediatrics 10 866295. (https://doi.org/10.3389/fped.2022.866295)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Henke E, Nandigama R & & Ergün S 2019 Extracellular matrix in the tumor microenvironment and its impact on cancer therapy. Frontiers in Molecular Biosciences 6 160. (https://doi.org/10.3389/fmolb.2019.00160)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Huang RX & & Zhou PK 2020 DNA damage response signaling pathways and targets for radiotherapy sensitization in cancer. Signal Transduction and Targeted Therapy 5 60. (https://doi.org/10.1038/s41392-020-0150-x)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Ibba A, Corrias F, Guzzetti C, Casula L, Salerno M, di Iorgi N, Tornese G, Patti G, Radetti G, Maghnie M, et al.2020 IGF1 for the diagnosis of growth hormone deficiency in children and adolescents: a reappraisal. Endocrine Connections 9 10951102. (https://doi.org/10.1530/EC-20-0347)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Isebaert SF, Swinnen JV, McBride WH & & Haustermans KM 2011 Insulin-like growth factor-type 1 receptor inhibitor NVP-AEW541 enhances radiosensitivity of PTEN wild-type but not PTEN-deficient human prostate cancer cells. International Journal of Radiation Oncology, Biology, Physics 81 239247. (https://doi.org/10.1016/j.ijrobp.2011.03.030)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Iwasa T, Okamoto I, Suzuki M, Hatashita E, Yamada Y, Fukuoka M, Ono K & & Nakagawa K 2009 Inhibition of insulin-like growth factor 1 receptor by CP-751,871 radiosensitizes non-small cell lung cancer cells. Clinical Cancer Research 15 51175125. (https://doi.org/10.1158/1078-0432.CCR-09-0478)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Jones B 2020 Clinical radiobiology of fast neutron therapy: what was learnt? Frontiers in Oncology 10 1537. (https://doi.org/10.3389/fonc.2020.01537)

  • Jorgensen EV, Schwartz ID, Hvizdala E, Barbosa J, Phuphanich S, Shulman DI, Root AW, Estrada J, Hu CS & & Bercu BB 1993 Neurotransmitter control of growth hormone secretion in children after cranial radiation therapy. Journal of Pediatric Endocrinology 6 131142.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Khan K, Araki K, Wang D, Li G, Li X, Zhang J, Xu W, Hoover RK, Lauter S, O'Malley B, et al.2010 Head and neck cancer radiosensitization by the novel poly(ADP-ribose) polymerase inhibitor GPI-15427. Head and Neck 32 381391. (https://doi.org/10.1002/hed.21195)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Kim BM, Hong Y, Lee S, Liu P, Lim JH, Lee YH, Lee TH, Chang KT & & Hong Y 2015 Therapeutic implications for overcoming radiation resistance in cancer therapy. International Journal of Molecular Sciences 16 2688026913. (https://doi.org/10.3390/ijms161125991)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Kranzinger M, Jones N, Rittinger O, Pilz P, Piotrowski WP, Manzl M, Galvan G & & Kogelnik HD 2001 Malignant glioma as a secondary malignant neoplasm after radiation therapy for craniopharyngioma: report of a case and review of reported cases. Onkologie 24 6672. (https://doi.org/10.1159/000050285)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Krull KR, Li C, Phillips NS, Cheung YT, Brinkman TM, Wilson CL, Armstrong GT, Khan RB, Merchant TE, Sabin ND, et al.2019 Growth hormone deficiency and neurocognitive function in adult survivors of childhood acute lymphoblastic leukemia. Cancer 125 17481755. (https://doi.org/10.1002/cncr.31975)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Lara PC, Bordón E, Rey A, Moreno M, Lloret M & & Henríquez-Hernández LA 2011 IGF-1R expression predicts clinical outcome in patients with locally advanced oral squamous cell carcinoma. Oral Oncology 47 615619. (https://doi.org/10.1016/j.oraloncology.2011.05.005)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Laron Z, Kauli R, Lapkina L & & Werner H 2017 IGF-I deficiency, longevity and cancer protection of patients with Laron syndrome. Mutation Research. Reviews in Mutation Research 772 123133. (https://doi.org/10.1016/j.mrrev.2016.08.002)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Lempereur L, Brambilla D, Scoto GM, D'Alcamo M, Goffin V, Crosta L, Palmucci T, Rampello L, Bernardini R & & Cantarella G 2003 Growth hormone protects human lymphocytes from irradiation-induced cell death. British Journal of Pharmacology 138 14111416. (https://doi.org/10.1038/sj.bjp.0705173)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Leung W, Ahn H, Rose SR, Phipps S, Smith T, Gan K, O'Connor M, Hale GA, Kasow KA, Barfield RC, et al.2007 A prospective cohort study of late sequelae of pediatric allogeneic hematopoietic stem cell transplantation. Medicine (Baltimore) 86 215224. (https://doi.org/10.1097/MD.0b013e31812f864d)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Li G, Nelsen C & & Hendrickson EA 2002 Ku86 is essential in human somatic cells. PNAS 99 832837. (https://doi.org/10.1073/pnas.022649699)

  • Link K, Moëll C, Garwicz S, Cavallin-Ståhl E, Björk J, Thilén U, Ahrén B & & Erfurth EM 2004 Growth hormone deficiency predicts cardiovascular risk in young adults treated for acute lymphoblastic leukemia in childhood. Journal of Clinical Endocrinology and Metabolism 89 50035012. (https://doi.org/10.1210/jc.2004-0126)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Lloret M, Lara PC, Bordón E, Pinar B, Rey A, Falcón O, Molano F & & Hernández MA 2007 IGF-1R expression in localized cervical carcinoma patients treated by radiochemotherapy. Gynecologic Oncology 106 811. (https://doi.org/10.1016/j.ygyno.2007.04.004)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Lu M, Flanagan JU, Langley RJ, Hay MP & & Perry JK 2019 Targeting growth hormone function: strategies and therapeutic applications. Signal Transduction and Targeted Therapy 4 3. (https://doi.org/10.1038/s41392-019-0036-y)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Macaulay VM, Salisbury AJ, Bohula EA, Playford MP, Smorodinsky NI & & Shiloh Y 2001 Downregulation of the type 1 insulin-like growth factor receptor in mouse melanoma cells is associated with enhanced radiosensitivity and impaired activation of Atm kinase. Oncogene 20 40294040. (https://doi.org/10.1038/sj.onc.1204565)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Mackenzie S, Craven T, Gattamaneni HR, Swindell R, Shalet SM & & Brabant G 2011 Long-term safety of growth hormone replacement after CNS irradiation. Journal of Clinical Endocrinology and Metabolism 96 27562761. (https://doi.org/10.1210/jc.2011-0112)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Madrid O, Varea S, Sanchez-Perez I, Gomez-Garcia L, De Miguel E, Gomez De Segura IA & & Perona R 2002 Growth hormone protects against radiotherapy-induced cell death. European Journal of Endocrinology 147 535541. (https://doi.org/10.1530/eje.0.1470535)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Mailhot Vega RB, Kim J, Bussière M, Hattangadi J, Hollander A, Michalski J, Tarbell NJ, Yock T & & MacDonald SM 2013 Cost effectiveness of proton therapy compared with photon therapy in the management of pediatric medulloblastoma. Cancer 119 42994307. (https://doi.org/10.1002/cncr.28322)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Mailhot Vega R, Kim J, Hollander A, Hattangadi-Gluth J, Michalski J, Tarbell NJ, Yock TI, Bussiere M & & MacDonald SM 2015 Cost effectiveness of proton versus photon radiation therapy with respect to the risk of growth hormone deficiency in children. Cancer 121 16941702. (https://doi.org/10.1002/cncr.29209)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Manda K, Glasow A, Paape D & & Hildebrandt G 2012 Effects of ionizing radiation on the immune system with special emphasis on the interaction of dendritic and T cells. Frontiers in Oncology 2 102. (https://doi.org/10.3389/fonc.2012.00102)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Merchant TE, Rose SR, Bosley C, Wu S, Xiong X & & Lustig RH 2011 Growth hormone secretion after conformal radiation therapy in pediatric patients with localized brain tumors. Journal of Clinical Oncology 29 47764780. (https://doi.org/10.1200/JCO.2011.37.9453)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Meyer S, Chibly AM, Burd R & & Limesand KH 2017 Insulin-like growth Factor-1-Mediated DNA repair in irradiated salivary glands is Sirtuin-1 dependent. Journal of Dental Research 96 225232. (https://doi.org/10.1177/0022034516677529)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Mizumoto M, Oshiro Y, Pan H, Wang F, Kaste SC, Gajjar A, Chemaitilly W & & Merchant TE 2020 Height after photon craniospinal irradiation in pediatric patients treated for central nervous system embryonal tumors. Pediatric Blood and Cancer 67 e28617. (https://doi.org/10.1002/pbc.28617)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Mojarrad M, Momeny M, Mansuri F, Abdolazimi Y, Tabrizi MH, Ghaffari SH, Tavangar SM & & Modarressi MH 2010 Autocrine human growth hormone expression leads to resistance of MCF-7 cells to tamoxifen. Medical Oncology 27 474480. (https://doi.org/10.1007/s12032-009-9237-5)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Molitch ME, Clemmons DR, Malozowski S, Merriam GR, Vance ML & Endocrine Society 2011 Evaluation and treatment of adult growth hormone deficiency: an Endocrine Society clinical practice guideline. Journal of Clinical Endocrinology and Metabolism 96 15871609. (https://doi.org/10.1210/jc.2011-0179).

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Morante J, Vallejo-Cremades MT, Gómez-García L, Vázquez I, Gómez-de-Segura IA, Sanchez M & & De Miguel E 2003 Differential action of growth hormone in irradiated tumoral and nontumoral intestinal tissue. Digestive Diseases and Sciences 48 21592166. (https://doi.org/10.1023/b:ddas.0000004520.71462.c9)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Morgan MA & & Lawrence TS 2015 Molecular pathways: overcoming radiation resistance by targeting DNA damage response pathways. Clinical Cancer Research 21 28982904. (https://doi.org/10.1158/1078-0432.CCR-13-3229)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Mulder RL, Kremer LC, van Santen HM, Ket JL, van Trotsenburg AS, Koning CC, Schouten-van Meeteren AY, Caron HN, Neggers SJ & & van Dalen EC 2009 Prevalence and risk factors of radiation-induced growth hormone deficiency in childhood cancer survivors: a systematic review. Cancer Treatment Reviews 35 616632. (https://doi.org/10.1016/j.ctrv.2009.06.004)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Multhoff G & & Radons J 2012 Radiation, inflammation, and immune responses in cancer. Frontiers in Oncology 2 58. (https://doi.org/10.3389/fonc.2012.00058)

  • Mylonas PG, Matsouka PT, Papandoniou EV, Vagianos C, Kalfarentzos F & & Alexandrides TK 2000 Growth hormone and insulin-like growth factor I protect intestinal cells from radiation induced apoptosis. Molecular and Cellular Endocrinology 160 115122. (https://doi.org/10.1016/s0303-7207(9900215-4)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Negrini S, Gorgoulis VG & & Halazonetis TD 2010 Genomic instability--an evolving hallmark of cancer. Nature Reviews. Molecular Cell Biology 11 220228. (https://doi.org/10.1038/nrm2858)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Ohno T 2013 Particle radiotherapy with carbon ion beams. EPMA Journal 4 9. (https://doi.org/10.1186/1878-5085-4-9)

  • Osuka S, Sampetrean O, Shimizu T, Saga I, Onishi N, Sugihara E, Okubo J, Fujita S, Takano S, Matsumura A, et al.2013 IGF1 receptor signaling regulates adaptive radioprotection in glioma stem cells. Stem Cells 31 627640. (https://doi.org/10.1002/stem.1328)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Patterson BC, Chen Y, Sklar CA, Neglia J, Yasui Y, Mertens A, Armstrong GT, Meadows A, Stovall M, Robison LL, et al.2014 Growth hormone exposure as a risk factor for the development of subsequent neoplasms of the central nervous system: a report from the childhood cancer survivor study. Journal of Clinical Endocrinology and Metabolism 99 20302037. (https://doi.org/10.1210/jc.2013-4159)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Pekic S, Stojanovic M & & Popovic V 2017 Controversies in the risk of neoplasia in GH deficiency. Best Practice and Research Clinical Endocrinology and Metabolism 31 3547. (https://doi.org/10.1016/j.beem.2017.02.004)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Petryk A, Baker KS, Frohnert B, Moran A, Chow L, Sinaiko AR, Steffen LM, Perkins JL, Zhang L, Hodges JS, et al.2013 Blunted response to a growth hormone stimulation test is associated with unfavorable cardiovascular risk factor profile in childhood cancer survivors. Pediatric Blood and Cancer 60 467473. (https://doi.org/10.1002/pbc.24308)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Podlutsky A, Valcarcel-Ares MN, Yancey K, Podlutskaya V, Nagykaldi E, Gautam T, Miller RA, Sonntag WE, Csiszar A & & Ungvari Z 2017 The GH/IGF-1 axis in a critical period early in life determines cellular DNA repair capacity by altering transcriptional regulation of DNA repair-related genes: implications for the developmental origins of cancer. GeroScience 39 147160. (https://doi.org/10.1007/s11357-017-9966-x)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Pollock NI & & Cohen LE 2021 Growth hormone deficiency and treatment in childhood cancer survivors. Frontiers in Endocrinology 12 745932. (https://doi.org/10.3389/fendo.2021.745932)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Prieto I, Gómez de Segura IA, García Grande A, García P, Carralero I & & de Miguel E 1998 Morphometric and proliferative effects of growth hormone on radiation enteritis in the rat. Revista Española de Enfermedades Digestivas 90 163173.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Qian Y, Basu R, Mathes SC, Arnett NA, Duran-Ortiz S, Funk KR, Brittain AL, Kulkarni P, Terry JC, Davis E, et al.2020 Growth hormone upregulates mediators of melanoma drug efflux and epithelial-to-mesenchymal transition in vitro and in vivo. Cancers 12 3640. (https://doi.org/10.3390/cancers12123640)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Raguso CA, Leverve X & & Pichard C 2002 Protective effects of recombinant growth hormone on intestinal mucosa in rats receiving abdominal radiotherapy. Clinical Nutrition 21 487490. (https://doi.org/10.1054/clnu.2002.0579)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Raju U, Molkentine DP, Valdecanas DR, Deorukhkar A, Mason KA, Buchholz TA, Meyn RE, Ang KK & & Skinner H 2015 Inhibition of EGFR or IGF-1R signaling enhances radiation response in head and neck cancer models but concurrent inhibition has no added benefit. Cancer Medicine 4 6574. (https://doi.org/10.1002/cam4.345)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Riesterer O, Yang Q, Raju U, Torres M, Molkentine D, Patel N, Valdecanas D, Milas L & & Ang KK 2011 Combination of anti-IGF-1R antibody A12 and ionizing radiation in upper respiratory tract cancers. International Journal of Radiation Oncology, Biology, Physics 79 11791187. (https://doi.org/10.1016/j.ijrobp.2010.10.003)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Rose SR, Carlsson M, Grimberg A, Aydin F, Albanese A, Hokken-Koelega ACS & & Camacho-Hubner C 2020 Response to GH treatment after radiation therapy depends on location of irradiation. Journal of Clinical Endocrinology and Metabolism 105 e3730e3741. (https://doi.org/10.1210/clinem/dgaa478)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Rosilio M, Blum WF, Edwards DJ, Shavrikova EP, Valle D, Lamberts SW, Erfurth EM, Webb SM, Ross RJ, Chihara K, et al.2004 Long-term improvement of quality of life during growth hormone (GH) replacement therapy in adults with GH deficiency, as measured by questions on life satisfaction-hypopituitarism (QLS-H). Journal of Clinical Endocrinology and Metabolism 89 16841693. (https://doi.org/10.1210/jc.2003-030134)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Ruchala M & & Wolinski K 2019 Health-related complications of acromegaly-risk of malignant neoplasms. Frontiers in Endocrinology 10 268. (https://doi.org/10.3389/fendo.2019.00268)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Rückert M, Flohr AS, Hecht M & & Gaipl US 2021 Radiotherapy and the immune system: more than just immune suppression. Stem Cells 39 11551165. (https://doi.org/10.1002/stem.3391)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Salvador Moreno N, Liu J, Haas KM, Parker LL, Chakraborty C, Kron SJ, Hodges K, Miller LD, Langefeld C, Robinson PJ, et al.2019 The nuclear structural protein NuMA is a negative regulator of 53BP1 in DNA double-strand break repair. Nucleic Acids Research 47 27032715. (https://doi.org/10.1093/nar/gkz138)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Sandfort V, Eke I & & Cordes N 2010 The role of the focal adhesion protein PINCH1 for the radiosensitivity of adhesion and suspension cell cultures. PLoS One 5 e13056. (https://doi.org/10.1371/journal.pone.0013056)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Schulz A, Meyer F, Dubrovska A & & Borgmann K 2019 Cancer stem cells and radioresistance: DNA repair and beyond. Cancers (Basel) 11 862. (https://doi.org/10.3390/cancers11060862)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Senra JM, Telfer BA, Cherry KE, McCrudden CM, Hirst DG, O'Connor MJ, Wedge SR & & Stratford IJ 2011 Inhibition of PARP-1 by olaparib (AZD2281) increases the radiosensitivity of a lung tumor xenograft. Molecular Cancer Therapeutics 10 19491958. (https://doi.org/10.1158/1535-7163.MCT-11-0278)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Seshacharyulu P, Halder S, Nimmakayala R, Rachagani S, Chaudhary S, Atri P, Chirravuri-Venkata R, Ouellette MM, Carmicheal J, Gautam SK, et al.2022 Disruption of FDPS/Rac1 axis radiosensitizes pancreatic ductal adenocarcinoma by attenuating DNA damage response and immunosuppressive signalling. EBiomedicine 75 103772. (https://doi.org/10.1016/j.ebiom.2021.103772)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Shalet SM, Beardwell CG, Pearson D & & Jones PH 1976 The effect of varying doses of cerebral irradiation on growth hormone production in childhood. Clinical Endocrinology 5 287290. (https://doi.org/10.1111/j.1365-2265.1976.tb01955.x)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Shimatsu A, Iwamoto N, Tanaka T, Teramoto A, Taketsuna M, Ihara K, Funai J, Irie M & & Chihara K 2015 Possible predictors for QOL improvement following GH replacement therapy in adult GHD. Endocrine Journal 62 749756. (https://doi.org/10.1507/endocrj.EJ14-0616)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Singh V, Gupta D & & Arora R 2015 NF-kB as a key player in regulation of cellular radiation responses and identification of radiation countermeasures. Discoveries 3 e35. (https://doi.org/10.15190/d.2015.27)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Sjögren K, Liu JL, Blad K, Skrtic S, Vidal O, Wallenius V, LeRoith D, Törnell J, Isaksson OG, Jansson JO, et al.1999 Liver-derived insulin-like growth factor I (IGF-I) is the principal source of IGF-I in blood but is not required for postnatal body growth in mice. PNAS 96 70887092. (https://doi.org/10.1073/pnas.96.12.7088)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Sklar CA 1997 Growth and neuroendocrine dysfunction following therapy for childhood cancer. Pediatric Clinics of North America 44 489503. (https://doi.org/10.1016/s0031-3955(0570487-9)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Sklar CA, Mertens AC, Mitby P, Occhiogrosso G, Qin J, Heller G, Yasui Y & & Robison LL 2002 Risk of disease recurrence and second neoplasms in survivors of childhood cancer treated with growth hormone: a report from the Childhood Cancer Survivor Study. Journal of Clinical Endocrinology and Metabolism 87 31363141. (https://doi.org/10.1210/jcem.87.7.8606)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Sklar CA, Antal Z, Chemaitilly W, Cohen LE, Follin C, Meacham LR & & Murad MH 2018 Hypothalamic-pituitary and growth disorders in survivors of childhood cancer: an Endocrine Society clinical practice guideline. Journal of Clinical Endocrinology and Metabolism 103 27612784. (https://doi.org/10.1210/jc.2018-01175)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Sørensen BS & & Horsman MR 2020 Tumor hypoxia: impact on radiation therapy and molecular pathways. Frontiers in Oncology 10 562. (https://doi.org/10.3389/fonc.2020.00562)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Stochholm K & & Kiess W 2018 Long-term safety of growth hormone-A combined registry analysis. Clinical Endocrinology 88 515528. (https://doi.org/10.1111/cen.13502)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Stochholm K, Gravholt CH, Laursen T, Laurberg P, Andersen M, Kristensen , Feldt-Rasmussen U, Christiansen JS, Frydenberg M & & Green A 2007 Mortality and GH deficiency: a nationwide study. European Journal of Endocrinology 157 918. (https://doi.org/10.1530/EJE-07-0013)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Swerdlow AJ, Cooke R, Beckers D, Borgström B, Butler G, Carel JC, Cianfarani S, Clayton P, Coste J, Deodati A, et al.2017 Cancer risks in patients treated with growth hormone in childhood: the SAGhE European cohort study. Journal of Clinical Endocrinology and Metabolism 102 16611672. (https://doi.org/10.1210/jc.2016-2046)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Swerdlow AJ, Cooke R, Beckers D, Butler G, Carel JC, Cianfarani S, Clayton P, Coste J, Deodati A, Ecosse E, et al.2019 Risk of meningioma in European patients treated with growth hormone in childhood: results from the SAGhE cohort. Journal of Clinical Endocrinology and Metabolism 104 658664. (https://doi.org/10.1210/jc.2018-01133)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Tafreshi NK, Doligalski ML, Tichacek CJ, Pandya DN, Budzevich MM, El-Haddad G, Khushalani NI, Moros EG, McLaughlin ML, Wadas TJ, et al.2019 Development of targeted alpha particle therapy for solid tumors. Molecules 24 4314. (https://doi.org/10.3390/molecules24234314)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Terzolo M, Puglisi S, Reimondo G, Dimopoulou C & & Stalla GK 2020 Thyroid and colorectal cancer screening in acromegaly patients: should it be different from that in the general population? European Journal of Endocrinology 183 D1D13. (https://doi.org/10.1530/EJE-19-1009)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Tezuka M, Watanabe H, Nakamura S, Yu D, Aung W, Sasaki T, Shibuya H & & Miura M 2001 Antiapoptotic activity is dispensable for insulin-like growth factor I receptor-mediated clonogenic radioresistance after gamma-irradiation. Clinical Cancer Research 7 32063214.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Thomas-Teinturier C, Oliver-Petit I, Pacquement H, Fresneau B, Allodji RS, Veres C, Bolle S, Berchery D, Demoor-Goldschmidt C, Haddy N, et al.2020 Influence of growth hormone therapy on the occurrence of a second neoplasm in survivors of childhood cancer. European Journal of Endocrinology 183 471480. (https://doi.org/10.1530/EJE-20-0369)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Tirosh A & & Shimon I 2017 Complications of acromegaly: thyroid and colon. Pituitary 20 7075. (https://doi.org/10.1007/s11102-016-0744-z)

  • Tommelein J, De Vlieghere E, Verset L, Melsens E, Leenders J, Descamps B, Debucquoy A, Vanhove C, Pauwels P, Gespach CP, et al.2018 Radiotherapy-activated cancer-associated fibroblasts promote tumor progression through paracrine IGF1R activation. Cancer Research 78 659670. (https://doi.org/10.1158/0008-5472.CAN-17-0524)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Toogood AA 2004 Endocrine consequences of brain irradiation. Growth Hormone and IGF Research 14(Supplement A) S118S124. (https://doi.org/10.1016/j.ghir.2004.03.038)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Toulany M 2019 Targeting DNA double-strand break repair pathways to improve radiotherapy response. Genes 10 25. (https://doi.org/10.3390/genes10010025)

  • Turner BC, Haffty BG, Narayanan L, Yuan J, Havre PA, Gumbs AA, Kaplan L, Burgaud JL, Carter D, Baserga R, et al.1997 Insulin-like growth factor-I receptor overexpression mediates cellular radioresistance and local breast cancer recurrence after lumpectomy and radiation. Cancer Research 57 30793083.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Turney BW, Kerr M, Chitnis MM, Lodhia K, Wang Y, Riedemann J, Rochester M, Protheroe AS, Brewster SF & & Macaulay VM 2012 Depletion of the type 1 IGF receptor delays repair of radiation-induced DNA double strand breaks. Radiotherapy and Oncology 103 402409. (https://doi.org/10.1016/j.radonc.2012.03.009)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • van Bunderen CC & & Olsson DS 2021 Growth hormone deficiency and replacement therapy in adults: impact on survival. Reviews in Endocrine and Metabolic Disorders 22 125133. (https://doi.org/10.1007/s11154-020-09599-w)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • van Dijk IW, van der Pal HJ, van Os RM, Roos YB, Sieswerda E, van Dalen EC, Ronckers CM, Oldenburger F, van Leeuwen FE, Caron HN, et al.2016 Risk of symptomatic stroke after radiation therapy for childhood cancer: a long-term follow-up cohort analysis. International Journal of Radiation Oncology, Biology, Physics 96 597605. (https://doi.org/10.1016/j.ijrobp.2016.03.049)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • van Iersel L, Li Z, Srivastava DK, Brinkman TM, Bjornard KL, Wilson CL, Green DM, Merchant TE, Pui CH, Howell RM, et al.2019 Hypothalamic-pituitary disorders in childhood cancer survivors: prevalence, risk factors and long-term health outcomes. Journal of Clinical Endocrinology and Metabolism 104 61016115. (https://doi.org/10.1210/jc.2019-00834)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • van Iersel L, van Santen HM, Potter B, Li Z, Conklin HM, Zhang H, Chemaitilly W & & Merchant TE 2020 Clinical impact of hypothalamic-pituitary disorders after conformal radiation therapy for pediatric low-grade glioma or ependymoma. Pediatric Blood and Cancer 67 e28723. (https://doi.org/10.1002/pbc.28723)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Vatner RE, Niemierko A, Misra M, Weyman EA, Goebel CP, Ebb DH, Jones RM, Huang MS, Mahajan A, Grosshans DR, et al.2018 Endocrine deficiency as a function of radiation dose to the hypothalamus and pituitary in pediatric and young adult patients with brain tumors. Journal of Clinical Oncology 36 28542862. (https://doi.org/10.1200/JCO.2018.78.1492)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Velegzhaninov IO, Belykh ES, Rasova EE, Pylina YI, Shadrin DM & & Klokov DY 2020 Radioresistance, DNA damage and DNA repair in cells with moderate overexpression of RPA1. Frontiers in Genetics 11 855. (https://doi.org/10.3389/fgene.2020.00855)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Veuger SJ, Hunter JE & & Durkacz BW 2009 Ionizing radiation-induced NF-kappaB activation requires PARP-1 function to confer radioresistance. Oncogene 28 832842. (https://doi.org/10.1038/onc.2008.439)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Wang YH, Wang ZX, Qiu Y, Xiong J, Chen YX, Miao DS & & De W 2009 Lentivirus-mediated RNAi knockdown of insulin-like growth factor-1 receptor inhibits growth, reduces invasion, and enhances radiosensitivity in human osteosarcoma cells. Molecular and Cellular Biochemistry 327 257266. (https://doi.org/10.1007/s11010-009-0064-y)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Wang G, Guo S, Zhang W, Li Z, Xu J, Li D, Wang Y & & Zhan Q 2020 A comprehensive analysis of alterations in DNA damage repair pathways reveals a potential way to enhance the radio-sensitivity of esophageal squamous cell cancer. Frontiers in Oncology 10 575711. (https://doi.org/10.3389/fonc.2020.575711)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Waraky A, Lin Y, Warsito D, Haglund F, Aleem E & & Larsson O 2017 Nuclear insulin-like growth factor 1 receptor phosphorylates proliferating cell nuclear antigen and rescues stalled replication forks after DNA damage. Journal of Biological Chemistry 292 1822718239. (https://doi.org/10.1074/jbc.M117.781492)

    • PubMed