Skip to main content
SpringerLink
Log in

Receptor Tyrosine Kinases as Targets for Enhancing Tumor Radiosensitivity

  • Chapter
  • First Online:
Increasing the Therapeutic Ratio of Radiotherapy

Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

  • 951 Accesses

Abstract

The advent of the modern era of molecularly targeted therapies in oncology has generated considerable excitement in the field of oncology. While there have been successes with molecularly targeted agents as monotherapies, most solid tumors display only a transient and modest response to single-targeted agents. As such, there has been significant effort in combining molecularly targeted agents with radiotherapy. Receptor tyrosine kinases (RTKs) play central roles in oncogenesis, stress sensitivity, tumor maintenance/progression, and clinical prognosis. Secondary to these roles, receptor tyrosine kinases are attractive targets for cancer therapy and specifically in combination with radiation therapy to enhance tumor radiosensitivity. Significant preclinical and clinical investigations have been performed to understand their roles in regulating the cellular response to radiation. A number of RTKs with relevance to radiation oncology have been identified including EGFR, VEGFR, IGF-1R, c-MET, and HER2. This chapter will highlight the preclinical and clinical findings associated with the combination of radiotherapy and inhibitors of the aforementioned receptors.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Druker BJ, Sawyers CL, Kantarjian H, Resta DJ, Reese SF, Ford JM, Capdeville R, Talpaz M (2001) Activity of a specific inhibitor of the BCR-ABL tyrosine kinase in the blast crisis of chronic myeloid leukemia and acute lymphoblastic leukemia with the Philadelphia chromosome. N Engl J Med 344(14):1038–1042. doi:10.1056/NEJM200104053441402

    Article  CAS  PubMed  Google Scholar 

  2. Nyati MK, Morgan MA, Feng FY, Lawrence TS (2006) Integration of EGFR inhibitors with radiochemotherapy. Nat Rev Cancer 6(11):876–885. doi:10.1038/nrc1953

    Article  CAS  PubMed  Google Scholar 

  3. Gschwind A, Fischer OM, Ullrich A (2004) The discovery of receptor tyrosine kinases: targets for cancer therapy. Nat Rev Cancer 4(5):361–370. doi:10.1038/nrc1360

    Article  CAS  PubMed  Google Scholar 

  4. Kim DW, Huamani J, Fu A, Hallahan DE (2006) Molecular strategies targeting the host component of cancer to enhance tumor response to radiation therapy. Int J Radiat Oncol Biol Phys 64(1):38–46. doi:10.1016/j.ijrobp.2005.02.008

    Article  CAS  PubMed  Google Scholar 

  5. Meyn RE, Munshi A, Haymach JV, Milas L, Ang KK (2009) Receptor signaling as a regulatory mechanism of DNA repair. Radiother Oncol 92(3):316–322. doi:10.1016/j.radonc.2009.06.031

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Herbst RS (2004) Review of epidermal growth factor receptor biology. Int J Radiat Oncol Biol Phys 59(2 Suppl):21–26. doi:10.1016/j.ijrobp.2003.11.041

    Article  CAS  PubMed  Google Scholar 

  7. Zips D, Krause M, Yaromina A, Dorfler A, Eicheler W, Schutze C, Gurtner K, Baumann M (2008) Epidermal growth factor receptor inhibitors for radiotherapy: biological rationale and preclinical results. J Pharm Pharmacol 60(8):1019–1028. doi:10.1211/jpp.60.8.0008

    Article  CAS  PubMed  Google Scholar 

  8. Uberall I, Kolar Z, Trojanec R, Berkovcova J, Hajduch M (2008) The status and role of ErbB receptors in human cancer. Exp Mol Pathol 84(2):79–89. doi:10.1016/j.yexmp.2007.12.002

    Article  CAS  PubMed  Google Scholar 

  9. Schmidt-Ullrich RK, Valerie K, Fogleman PB, Walters J (1996) Radiation-induced autophosphorylation of epidermal growth factor receptor in human malignant mammary and squamous epithelial cells. Radiat Res 145(1):81–85

    Article  CAS  PubMed  Google Scholar 

  10. Contessa JN, Reardon DB, Todd D, Dent P, Mikkelsen RB, Valerie K, Bowers GD, Schmidt-Ullrich RK (1999) The inducible expression of dominant-negative epidermal growth factor receptor-CD533 results in radiosensitization of human mammary carcinoma cells. Clin Cancer Res 5(2):405–411

    CAS  PubMed  Google Scholar 

  11. Li W, Li F, Huang Q, Frederick B, Bao S, Li CY (2008) Noninvasive imaging and quantification of epidermal growth factor receptor kinase activation in vivo. Cancer Res 68(13):4990–4997. doi:10.1158/0008-5472.CAN-07-5984

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Dent P, Reardon DB, Park JS, Bowers G, Logsdon C, Valerie K, Schmidt-Ullrich R (1999) Radiation-induced release of transforming growth factor alpha activates the epidermal growth factor receptor and mitogen-activated protein kinase pathway in carcinoma cells, leading to increased proliferation and protection from radiation-induced cell death. Mol Biol Cell 10(8):2493–2506

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Sturla LM, Amorino G, Alexander MS, Mikkelsen RB, Valerie K, Schmidt-Ullrichr RK (2005) Requirement of Tyr-992 and Tyr-1173 in phosphorylation of the epidermal growth factor receptor by ionizing radiation and modulation by SHP2. J Biol Chem 280(15):14597–14604. doi:10.1074/jbc.M413287200

    Article  CAS  PubMed  Google Scholar 

  14. Hennessy BT, Smith DL, Ram PT, Lu Y, Mills GB (2005) Exploiting the PI3K/AKT pathway for cancer drug discovery. Nat Rev Drug Discov 4(12):988–1004. doi:10.1038/nrd1902

    Article  CAS  PubMed  Google Scholar 

  15. Irwin ME, Bohin N, Boerner JL (2011) Src family kinases mediate epidermal growth factor receptor signaling from lipid rafts in breast cancer cells. Cancer Biol Ther 12(8):718–726. doi:10.4161/cbt.12.8.16907

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Oliva JL, Griner EM, Kazanietz MG (2005) PKC isozymes and diacylglycerol-regulated proteins as effectors of growth factor receptors. Growth Factors 23(4):245–252. doi:10.1080/08977190500366043

    Article  CAS  PubMed  Google Scholar 

  17. Schmidt-Ullrich RK, Mikkelsen RB, Dent P, Todd DG, Valerie K, Kavanagh BD, Contessa JN, Rorrer WK, Chen PB (1997) Radiation-induced proliferation of the human A431 squamous carcinoma cells is dependent on EGFR tyrosine phosphorylation. Oncogene 15(10):1191–1197. doi:10.1038/sj.onc.1201275

    Article  CAS  PubMed  Google Scholar 

  18. Sebolt-Leopold JS, Herrera R (2004) Targeting the mitogen-activated protein kinase cascade to treat cancer. Nat Rev Cancer 4(12):937–947. doi:10.1038/nrc1503

    Article  CAS  PubMed  Google Scholar 

  19. Chen DJ, Nirodi CS (2007) The epidermal growth factor receptor: a role in repair of radiation-induced DNA damage. Clin Cancer Res 13(22 Pt 1):6555–6560. doi:10.1158/1078-0432.CCR-07-1610

    Article  CAS  PubMed  Google Scholar 

  20. Hayman TJ, Kramp T, Kahn J, Jamal M, Camphausen K, Tofilon PJ (2013) Competitive but not allosteric mTOR kinase inhibition enhances tumor cell radiosensitivity. Transl Oncol 6(3):355–362

    Article  PubMed  PubMed Central  Google Scholar 

  21. Hayman TJ, Wahba A, Rath BH, Bae H, Kramp T, Shankavaram UT, Camphausen K, Tofilon PJ (2014) The ATP-competitive mTOR inhibitor INK128 enhances in vitro and in vivo radiosensitivity of pancreatic carcinoma cells. Clin Cancer Res 20(1):110–119. doi:10.1158/1078-0432.CCR-13-2136

    Article  CAS  PubMed  Google Scholar 

  22. Toulany M, Rodemann HP (2010) Membrane receptor signaling and control of DNA repair after exposure to ionizing radiation. Nuklearmed Nucl Med 49(Suppl 1):S26–S30

    CAS  Google Scholar 

  23. Bonner JA, Trummell HQ, Willey CD, Plants BA, Raisch KP (2009) Inhibition of STAT-3 results in radiosensitization of human squamous cell carcinoma. Radiother Oncol 92(3):339–344. doi:10.1016/j.radonc.2009.06.022

    Article  CAS  PubMed  Google Scholar 

  24. Willey CD, Xiao D, Tu T, Kim KW, Moretti L, Niermann KJ, Tawtawy MN, Quarles CC, Lu B (2010) Enzastaurin (LY317615), a protein kinase C beta selective inhibitor, enhances antiangiogenic effect of radiation. Int J Radiat Oncol Biol Phys 77(5):1518–1526. doi:10.1016/j.ijrobp.2009.06.044

    Article  CAS  PubMed  Google Scholar 

  25. Mendelsohn J (2001) The epidermal growth factor receptor as a target for cancer therapy. Endocr Relat Cancer 8(1):3–9

    Article  CAS  PubMed  Google Scholar 

  26. Ruddel J, Wennekes VE, Meissner W, Werner JA, Mandic R (2010) EGF-dependent induction of BCL-xL and p21CIP1/WAF1 is highly variable in HNSCC cells–implications for EGFR-targeted therapies. Anticancer Res 30(11):4579–4585

    PubMed  Google Scholar 

  27. Cohen RB (2014) Current challenges and clinical investigations of epidermal growth factor receptor (EGFR)- and ErbB family-targeted agents in the treatment of head and neck squamous cell carcinoma (HNSCC). Cancer Treat Rev 40(4):567–577. doi:10.1016/j.ctrv.2013.10.002

    Article  CAS  PubMed  Google Scholar 

  28. Kris MG, Natale RB, Herbst RS, Lynch TJ Jr, Prager D, Belani CP, Schiller JH, Kelly K, Spiridonidis H, Sandler A, Albain KS, Cella D, Wolf MK, Averbuch SD, Ochs JJ, Kay AC (2003) Efficacy of gefitinib, an inhibitor of the epidermal growth factor receptor tyrosine kinase, in symptomatic patients with non-small cell lung cancer: a randomized trial. JAMA 290(16):2149–2158. doi:10.1001/jama.290.16.2149

    Article  CAS  PubMed  Google Scholar 

  29. Ellis PM, Coakley N, Feld R, Kuruvilla S, Ung YC (2015) Use of the epidermal growth factor receptor inhibitors gefitinib, erlotinib, afatinib, dacomitinib, and icotinib in the treatment of non-small-cell lung cancer: a systematic review. Curr Oncol 22(3):e183–e215. doi:10.3747/co.22.2566

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Kwok TT, Sutherland RM (1989) Enhancement of sensitivity of human squamous carcinoma cells to radiation by epidermal growth factor. J Natl Cancer Inst 81(13):1020–1024

    Article  CAS  PubMed  Google Scholar 

  31. Bonner JA, Maihle NJ, Folven BR, Christianson TJ, Spain K (1994) The interaction of epidermal growth factor and radiation in human head and neck squamous cell carcinoma cell lines with vastly different radiosensitivities. Int J Radiat Oncol Biol Phys 29(2):243–247

    Article  CAS  PubMed  Google Scholar 

  32. Balaban N, Moni J, Shannon M, Dang L, Murphy E, Goldkorn T (1996) The effect of ionizing radiation on signal transduction: antibodies to EGF receptor sensitize A431 cells to radiation. Biochim Biophys Acta 1314(1-2):147–156

    Article  CAS  PubMed  Google Scholar 

  33. Sheridan MT, O'Dwyer T, Seymour CB, Mothersill CE (1997) Potential indicators of radiosensitivity in squamous cell carcinoma of the head and neck. Radiat Oncol Investig 5(4):180–186. doi:10.1002/(SICI)1520-6823(1997)5:4<180::AID-ROI3>3.0.CO;2-U

    Article  CAS  PubMed  Google Scholar 

  34. Milas L, Fan Z, Andratschke NH, Ang KK (2004) Epidermal growth factor receptor and tumor response to radiation: in vivo preclinical studies. Int J Radiat Oncol Biol Phys 58(3):966–971. doi:10.1016/j.ijrobp.2003.08.035

    Article  CAS  PubMed  Google Scholar 

  35. Akimoto T, Hunter NR, Buchmiller L, Mason K, Ang KK, Milas L (1999) Inverse relationship between epidermal growth factor receptor expression and radiocurability of murine carcinomas. Clin Cancer Res 5(10):2884–2890

    CAS  PubMed  Google Scholar 

  36. Ang KK, Berkey BA, Tu X, Zhang HZ, Katz R, Hammond EH, Fu KK, Milas L (2002) Impact of epidermal growth factor receptor expression on survival and pattern of relapse in patients with advanced head and neck carcinoma. Cancer Res 62(24):7350–7356

    CAS  PubMed  Google Scholar 

  37. Goldkorn T, Balaban N, Shannon M, Matsukuma K (1997) EGF receptor phosphorylation is affected by ionizing radiation. Biochim Biophys Acta 1358(3):289–299

    Article  CAS  PubMed  Google Scholar 

  38. Contessa JN, Hampton J, Lammering G, Mikkelsen RB, Dent P, Valerie K, Schmidt-Ullrich RK (2002) Ionizing radiation activates Erb-B receptor dependent Akt and p70 S6 kinase signaling in carcinoma cells. Oncogene 21(25):4032–4041. doi:10.1038/sj.onc.1205500

    Article  CAS  PubMed  Google Scholar 

  39. Lammering G, Hewit TH, Hawkins WT, Contessa JN, Reardon DB, Lin PS, Valerie K, Dent P, Mikkelsen RB, Schmidt-Ullrich RK (2001) Epidermal growth factor receptor as a genetic therapy target for carcinoma cell radiosensitization. J Natl Cancer Inst 93(12):921–929

    Article  CAS  PubMed  Google Scholar 

  40. Huang SM, Bock JM, Harari PM (1999) Epidermal growth factor receptor blockade with C225 modulates proliferation, apoptosis, and radiosensitivity in squamous cell carcinomas of the head and neck. Cancer Res 59(8):1935–1940

    CAS  PubMed  Google Scholar 

  41. Gan HK, Burgess AW, Clayton AH, Scott AM (2012) Targeting of a conformationally exposed, tumor-specific epitope of EGFR as a strategy for cancer therapy. Cancer Res 72(12):2924–2930. doi:10.1158/0008-5472.CAN-11-3898

    Article  CAS  PubMed  Google Scholar 

  42. ClinicalTrials.gov [database on the Internet] (2000) National Library of Medicine (US). National Library of Medicine (US), Bethesda, MD. Available via National Library of Medicine (US). http://clinicaltrials.gov/. Accessed 1 Aug 2015

  43. Hatanpaa KJ, Burma S, Zhao D, Habib AA (2010) Epidermal growth factor receptor in glioma: signal transduction, neuropathology, imaging, and radioresistance. Neoplasia 12(9):675–684

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Raben D, Helfrich B, Bunn PA Jr (2004) Targeted therapies for non-small-cell lung cancer: biology, rationale, and preclinical results from a radiation oncology perspective. Int J Radiat Oncol Biol Phys 59(2 Suppl):27–38. doi:10.1016/j.ijrobp.2004.01.054

    Article  CAS  PubMed  Google Scholar 

  45. Rao GS, Murray S, Ethier SP (2000) Radiosensitization of human breast cancer cells by a novel ErbB family receptor tyrosine kinase inhibitor. Int J Radiat Oncol Biol Phys 48(5):1519–1528

    Article  CAS  PubMed  Google Scholar 

  46. Krause M, Schutze C, Petersen C, Pimentel N, Hessel F, Harstrick A, Baumann M (2005) Different classes of EGFR inhibitors may have different potential to improve local tumour control after fractionated irradiation: a study on C225 in FaDu hSCC. Radiother Oncol 74(2):109–115. doi:10.1016/j.radonc.2004.10.011

    Article  CAS  PubMed  Google Scholar 

  47. Solomon B, Hagekyriakou J, Trivett MK, Stacker SA, McArthur GA, Cullinane C (2003) EGFR blockade with ZD1839 (“Iressa”) potentiates the antitumor effects of single and multiple fractions of ionizing radiation in human A431 squamous cell carcinoma. Epidermal growth factor receptor. Int J Radiat Oncol Biol Phys 55(3):713–723

    Article  CAS  PubMed  Google Scholar 

  48. Shintani S, Li C, Mihara M, Terakado N, Yano J, Nakashiro K, Hamakawa H (2003) Enhancement of tumor radioresponse by combined treatment with gefitinib (Iressa, ZD1839), an epidermal growth factor receptor tyrosine kinase inhibitor, is accompanied by inhibition of DNA damage repair and cell growth in oral cancer. Int J Cancer 107(6):1030–1037. doi:10.1002/ijc.11437

    Article  CAS  PubMed  Google Scholar 

  49. Cuneo KC, Nyati MK, Ray D, Lawrence TS (2015) EGFR targeted therapies and radiation: Optimizing efficacy by appropriate drug scheduling and patient selection. Pharmacol Ther. doi:10.1016/j.pharmthera.2015.07.002

    PubMed  PubMed Central  Google Scholar 

  50. Bonner JA, Harari PM, Giralt J, Azarnia N, Shin DM, Cohen RB, Jones CU, Sur R, Raben D, Jassem J, Ove R, Kies MS, Baselga J, Youssoufian H, Amellal N, Rowinsky EK, Ang KK (2006) Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med 354(6):567–578. doi:10.1056/NEJMoa053422

    Article  CAS  PubMed  Google Scholar 

  51. Ang KK, Zhang Q, Rosenthal DI, Nguyen-Tan PF, Sherman EJ, Weber RS, Galvin JM, Bonner JA, Harris J, El-Naggar AK, Gillison ML, Jordan RC, Konski AA, Thorstad WL, Trotti A, Beitler JJ, Garden AS, Spanos WJ, Yom SS, Axelrod RS (2014) Randomized phase III trial of concurrent accelerated radiation plus cisplatin with or without cetuximab for stage III to IV head and neck carcinoma: RTOG 0522. J Clin Oncol 32(27):2940–2950. doi:10.1200/JCO.2013.53.5633

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Bradley JD, Paulus R, Komaki R, Masters G, Blumenschein G, Schild S, Bogart J, Hu C, Forster K, Magliocco A, Kavadi V, Garces YI, Narayan S, Iyengar P, Robinson C, Wynn RB, Koprowski C, Meng J, Beitler J, Gaur R, Curran W Jr, Choy H (2015) Standard-dose versus high-dose conformal radiotherapy with concurrent and consolidation carboplatin plus paclitaxel with or without cetuximab for patients with stage IIIA or IIIB non-small-cell lung cancer (RTOG 0617): a randomised, two-by-two factorial phase 3 study. Lancet Oncol 16(2):187–199. doi:10.1016/S1470-2045(14)71207-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Riaz N, Sherman EJ, Fury M, Lee N (2013) Should cetuximab replace Cisplatin for definitive chemoradiotherapy in locally advanced head and neck cancer? J Clin Oncol 31(2):287–288. doi:10.1200/JCO.2012.46.9049

    Article  CAS  PubMed  Google Scholar 

  54. Elie C, Geay JF, Morcos M, Le Tourneau A, Girre V, Broet P, Marmey B, Chauvenet L, Audouin J, Pujade-Lauraine E, Camilleri-Broet S (2004) Lack of relationship between EGFR-1 immunohistochemical expression and prognosis in a multicentre clinical trial of 93 patients with advanced primary ovarian epithelial cancer (GINECO group). Br J Cancer 91(3):470–475. doi:10.1038/sj.bjc.6601961

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Chung KY, Shia J, Kemeny NE, Shah M, Schwartz GK, Tse A, Hamilton A, Pan D, Schrag D, Schwartz L, Klimstra DS, Fridman D, Kelsen DP, Saltz LB (2005) Cetuximab shows activity in colorectal cancer patients with tumors that do not express the epidermal growth factor receptor by immunohistochemistry. J Clin Oncol 23(9):1803–1810. doi:10.1200/JCO.2005.08.037

    Article  CAS  PubMed  Google Scholar 

  56. Ferrara N, Gerber HP, LeCouter J (2003) The biology of VEGF and its receptors. Nat Med 9(6):669–676. doi:10.1038/nm0603-669

    Article  CAS  PubMed  Google Scholar 

  57. Goel HL, Mercurio AM (2013) VEGF targets the tumour cell. Nat Rev Cancer 13(12):871–882. doi:10.1038/nrc3627

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Kabbinavar F, Hurwitz HI, Fehrenbacher L, Meropol NJ, Novotny WF, Lieberman G, Griffing S, Bergsland E (2003) Phase II, randomized trial comparing bevacizumab plus fluorouracil (FU)/leucovorin (LV) with FU/LV alone in patients with metastatic colorectal cancer. J Clin Oncol 21(1):60–65

    Article  CAS  PubMed  Google Scholar 

  59. Ferrara N, Hillan KJ, Gerber HP, Novotny W (2004) Discovery and development of bevacizumab, an anti-VEGF antibody for treating cancer. Nat Rev Drug Discov 3(5):391–400. doi:10.1038/nrd1381

    Article  CAS  PubMed  Google Scholar 

  60. O'Reilly MS (2006) Radiation combined with antiangiogenic and antivascular agents. Semin Radiat Oncol 16(1):45–50. doi:10.1016/j.semradonc.2005.08.006

    Article  PubMed  Google Scholar 

  61. Teicher BA, Dupuis N, Kusomoto T, Robinson MF, Liu F, Menon K, Coleman CN (1994) Antiangiogenic agents can increase tumor oxygenation and response to radiation therapy. Radiat Oncol Investig 2(6):269–276

    Article  CAS  Google Scholar 

  62. Wachsberger PR, Lawrence YR, Liu Y, Daroczi B, Xu X, Dicker AP (2012) Epidermal growth factor receptor expression modulates antitumor efficacy of vandetanib or cediranib combined with radiotherapy in human glioblastoma xenografts. Int J Radiat Oncol Biol Phys 82(1):483–491. doi:10.1016/j.ijrobp.2010.09.019

    Article  CAS  PubMed  Google Scholar 

  63. Mauceri HJ, Hanna NN, Beckett MA, Gorski DH, Staba MJ, Stellato KA, Bigelow K, Heimann R, Gately S, Dhanabal M, Soff GA, Sukhatme VP, Kufe DW, Weichselbaum RR (1998) Combined effects of angiostatin and ionizing radiation in antitumour therapy. Nature 394(6690):287–291. doi:10.1038/28412

    Article  CAS  PubMed  Google Scholar 

  64. Gorski DH, Beckett MA, Jaskowiak NT, Calvin DP, Mauceri HJ, Salloum RM, Seetharam S, Koons A, Hari DM, Kufe DW, Weichselbaum RR (1999) Blockage of the vascular endothelial growth factor stress response increases the antitumor effects of ionizing radiation. Cancer Res 59(14):3374–3378

    CAS  PubMed  Google Scholar 

  65. Wachsberger P, Burd R, Dicker AP (2003) Tumor response to ionizing radiation combined with antiangiogenesis or vascular targeting agents: exploring mechanisms of interaction. Clin Cancer Res 9(6):1957–1971

    CAS  PubMed  Google Scholar 

  66. Kozin SV, Boucher Y, Hicklin DJ, Bohlen P, Jain RK, Suit HD (2001) Vascular endothelial growth factor receptor-2-blocking antibody potentiates radiation-induced long-term control of human tumor xenografts. Cancer Res 61(1):39–44

    CAS  PubMed  Google Scholar 

  67. Winkler F, Kozin SV, Tong RT, Chae SS, Booth MF, Garkavtsev I, Xu L, Hicklin DJ, Fukumura D, di Tomaso E, Munn LL, Jain RK (2004) Kinetics of vascular normalization by VEGFR2 blockade governs brain tumor response to radiation: role of oxygenation, angiopoietin-1, and matrix metalloproteinases. Cancer Cell 6(6):553–563. doi:10.1016/j.ccr.2004.10.011

    CAS  PubMed  Google Scholar 

  68. Jain RK (2001) Normalizing tumor vasculature with anti-angiogenic therapy: a new paradigm for combination therapy. Nat Med 7(9):987–989. doi:10.1038/nm0901-987

    Article  CAS  PubMed  Google Scholar 

  69. Searle EJ, Illidge TM, Stratford IJ (2014) Emerging opportunities for the combination of molecularly targeted drugs with radiotherapy. Clin Oncol (R Coll Radiol) 26(5):266–276. doi:10.1016/j.clon.2014.02.006

    Article  CAS  Google Scholar 

  70. Gilbert MR, Dignam JJ, Armstrong TS, Wefel JS, Blumenthal DT, Vogelbaum MA, Colman H, Chakravarti A, Pugh S, Won M, Jeraj R, Brown PD, Jaeckle KA, Schiff D, Stieber VW, Brachman DG, Werner-Wasik M, Tremont-Lukats IW, Sulman EP, Aldape KD, Curran WJ Jr, Mehta MP (2014) A randomized trial of bevacizumab for newly diagnosed glioblastoma. N Engl J Med 370(8):699–708. doi:10.1056/NEJMoa1308573

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Chinot OL, Wick W, Mason W, Henriksson R, Saran F, Nishikawa R, Carpentier AF, Hoang-Xuan K, Kavan P, Cernea D, Brandes AA, Hilton M, Abrey L, Cloughesy T (2014) Bevacizumab plus radiotherapy-temozolomide for newly diagnosed glioblastoma. N Engl J Med 370(8):709–722. doi:10.1056/NEJMoa1308345

    Article  CAS  PubMed  Google Scholar 

  72. Jain RK, Duda DG, Clark JW, Loeffler JS (2006) Lessons from phase III clinical trials on anti-VEGF therapy for cancer. Nat Clin Pract Oncol 3(1):24–40. doi:10.1038/ncponc0403

    Article  CAS  PubMed  Google Scholar 

  73. Dietrich J, Wang D, Batchelor TT (2009) Cediranib: profile of a novel anti-angiogenic agent in patients with glioblastoma. Expert Opin Investig Drugs 18(10):1549–1557. doi:10.1517/13543780903183528

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Holderfield MT, Hughes CC (2008) Crosstalk between vascular endothelial growth factor, notch, and transforming growth factor-beta in vascular morphogenesis. Circ Res 102(6):637–652. doi:10.1161/CIRCRESAHA.107.167171

    Article  CAS  PubMed  Google Scholar 

  75. Birchmeier C, Birchmeier W, Gherardi E, Vande Woude GF (2003) Met, metastasis, motility and more. Nat Rev Mol Cell Biol 4(12):915–925. doi:10.1038/nrm1261

    Article  CAS  PubMed  Google Scholar 

  76. Ponzetto C, Bardelli A, Zhen Z, Maina F, dalla Zonca P, Giordano S, Graziani A, Panayotou G, Comoglio PM (1994) A multifunctional docking site mediates signaling and transformation by the hepatocyte growth factor/scatter factor receptor family. Cell 77 (2):261–271

    Google Scholar 

  77. Bhardwaj V, Cascone T, Cortez MA, Amini A, Evans J, Komaki RU, Heymach JV, Welsh JW (2013) Modulation of c-Met signaling and cellular sensitivity to radiation: potential implications for therapy. Cancer 119(10):1768–1775. doi:10.1002/cncr.27965

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Sipeki S, Bander E, Buday L, Farkas G, Bacsy E, Ways DK, Farago A (1999) Phosphatidylinositol 3-kinase contributes to Erk1/Erk2 MAP kinase activation associated with hepatocyte growth factor-induced cell scattering. Cell Signal 11(12):885–890

    Article  CAS  PubMed  Google Scholar 

  79. Stoker M, Gherardi E, Perryman M, Gray J (1987) Scatter factor is a fibroblast-derived modulator of epithelial cell mobility. Nature 327(6119):239–242. doi:10.1038/327239a0

    Article  CAS  PubMed  Google Scholar 

  80. Rosen EM, Knesel J, Goldberg ID, Jin L, Bhargava M, Joseph A, Zitnik R, Wines J, Kelley M, Rockwell S (1994) Scatter factor modulates the metastatic phenotype of the EMT6 mouse mammary tumor. Int J Cancer 57(5):706–714

    Article  CAS  PubMed  Google Scholar 

  81. Sonnenberg E, Meyer D, Weidner KM, Birchmeier C (1993) Scatter factor/hepatocyte growth factor and its receptor, the c-met tyrosine kinase, can mediate a signal exchange between mesenchyme and epithelia during mouse development. J Cell Biol 123(1):223–235

    Article  CAS  PubMed  Google Scholar 

  82. Santos OF, Barros EJ, Yang XM, Matsumoto K, Nakamura T, Park M, Nigam SK (1994) Involvement of hepatocyte growth factor in kidney development. Dev Biol 163(2):525–529. doi:10.1006/dbio.1994.1169

    Article  CAS  PubMed  Google Scholar 

  83. Raghav KP, Wang W, Liu S, Chavez-MacGregor M, Meng X, Hortobagyi GN, Mills GB, Meric-Bernstam F, Blumenschein GR Jr, Gonzalez-Angulo AM (2012) cMET and phospho-cMET protein levels in breast cancers and survival outcomes. Clin Cancer Res 18(8):2269–2277. doi:10.1158/1078-0432.CCR-11-2830

    Article  CAS  PubMed  Google Scholar 

  84. Moriyama T, Kataoka H, Koono M, Wakisaka S (1999) Expression of hepatocyte growth factor/scatter factor and its receptor c-Met in brain tumors: evidence for a role in progression of astrocytic tumors (Review). Int J Mol Med 3(5):531–536

    CAS  PubMed  Google Scholar 

  85. Koochekpour S, Jeffers M, Rulong S, Taylor G, Klineberg E, Hudson EA, Resau JH, Vande Woude GF (1997) Met and hepatocyte growth factor/scatter factor expression in human gliomas. Cancer Res 57(23):5391–5398

    CAS  PubMed  Google Scholar 

  86. Inno A, Di Salvatore M, Cenci T, Martini M, Orlandi A, Strippoli A, Ferrara AM, Bagala C, Cassano A, Larocca LM, Barone C (2011) Is there a role for IGF1R and c-MET pathways in resistance to cetuximab in metastatic colorectal cancer? Clin Colorectal Cancer 10(4):325–332. doi:10.1016/j.clcc.2011.03.028

    Article  CAS  PubMed  Google Scholar 

  87. Cheng TL, Chang MY, Huang SY, Sheu CC, Kao EL, Cheng YJ, Chong IW (2005) Overexpression of circulating c-met messenger RNA is significantly correlated with nodal stage and early recurrence in non-small cell lung cancer. Chest 128(3):1453–1460. doi:10.1378/chest.128.3.1453

    Article  CAS  PubMed  Google Scholar 

  88. Maulik G, Kijima T, Ma PC, Ghosh SK, Lin J, Shapiro GI, Schaefer E, Tibaldi E, Johnson BE, Salgia R (2002) Modulation of the c-Met/hepatocyte growth factor pathway in small cell lung cancer. Clin Cancer Res 8(2):620–627

    CAS  PubMed  Google Scholar 

  89. Masuya D, Huang C, Liu D, Nakashima T, Kameyama K, Haba R, Ueno M, Yokomise H (2004) The tumour-stromal interaction between intratumoral c-Met and stromal hepatocyte growth factor associated with tumour growth and prognosis in non-small-cell lung cancer patients. Br J Cancer 90(8):1555–1562. doi:10.1038/sj.bjc.6601718

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Nakamura Y, Niki T, Goto A, Morikawa T, Miyazawa K, Nakajima J, Fukayama M (2007) c-Met activation in lung adenocarcinoma tissues: an immunohistochemical analysis. Cancer Sci 98(7):1006–1013. doi:10.1111/j.1349-7006.2007.00493.x

    Article  CAS  PubMed  Google Scholar 

  91. Liu Y, Li Q, Zhu L (2012) Expression of the hepatocyte growth factor and c-Met in colon cancer: correlation with clinicopathological features and overall survival. Tumori 98(1):105–112. doi:10.1700/1053.11508

    PubMed  Google Scholar 

  92. Fan S, Wang JA, Yuan RQ, Rockwell S, Andres J, Zlatapolskiy A, Goldberg ID, Rosen EM (1998) Scatter factor protects epithelial and carcinoma cells against apoptosis induced by DNA-damaging agents. Oncogene 17(2):131–141. doi:10.1038/sj.onc.1201943

    Article  CAS  PubMed  Google Scholar 

  93. Fan S, Ma YX, Wang JA, Yuan RQ, Meng Q, Cao Y, Laterra JJ, Goldberg ID, Rosen EM (2000) The cytokine hepatocyte growth factor/scatter factor inhibits apoptosis and enhances DNA repair by a common mechanism involving signaling through phosphatidyl inositol 3' kinase. Oncogene 19(18):2212–2223. doi:10.1038/sj.onc.1203566

    Article  CAS  PubMed  Google Scholar 

  94. Aebersold DM, Kollar A, Beer KT, Laissue J, Greiner RH, Djonov V (2001) Involvement of the hepatocyte growth factor/scatter factor receptor c-met and of Bcl-xL in the resistance of oropharyngeal cancer to ionizing radiation. Int J Cancer 96(1):41–54

    Article  CAS  PubMed  Google Scholar 

  95. De Bacco F, Luraghi P, Medico E, Reato G, Girolami F, Perera T, Gabriele P, Comoglio PM, Boccaccio C (2011) Induction of MET by ionizing radiation and its role in radioresistance and invasive growth of cancer. J Natl Cancer Inst 103(8):645–661. doi:10.1093/jnci/djr093

    Article  PubMed  CAS  Google Scholar 

  96. Qian LW, Mizumoto K, Inadome N, Nagai E, Sato N, Matsumoto K, Nakamura T, Tanaka M (2003) Radiation stimulates HGF receptor/c-Met expression that leads to amplifying cellular response to HGF stimulation via upregulated receptor tyrosine phosphorylation and MAP kinase activity in pancreatic cancer cells. Int J Cancer 104(5):542–549. doi:10.1002/ijc.10997

    Article  CAS  PubMed  Google Scholar 

  97. Sheng-Hua C, Yan-Bin M, Zhi-An Z, Hong Z, Dong-Fu F, Zhi-Qiang L, Xian-Hou Y (2007) Radiation-enhanced hepatocyte growth factor secretion in malignant glioma cell lines. Surg Neurol 68(6):610–613. doi:10.1016/j.surneu.2006.12.050, discussion 613-614

    Article  PubMed  Google Scholar 

  98. Schweigerer L, Rave-Frank M, Schmidberger H, Hecht M (2005) Sublethal irradiation promotes invasiveness of neuroblastoma cells. Biochem Biophys Res Commun 330(3):982–988. doi:10.1016/j.bbrc.2005.03.068

    Article  CAS  PubMed  Google Scholar 

  99. Welsh JW, Mahadevan D, Ellsworth R, Cooke L, Bearss D, Stea B (2009) The c-Met receptor tyrosine kinase inhibitor MP470 radiosensitizes glioblastoma cells. Radiat Oncol 4:69. doi:10.1186/1748-717X-4-69

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  100. Medova M, Aebersold DM, Blank-Liss W, Streit B, Medo M, Aebi S, Zimmer Y (2010) MET inhibition results in DNA breaks and synergistically sensitizes tumor cells to DNA-damaging agents potentially by breaching a damage-induced checkpoint arrest. Genes Cancer 1(10):1053–1062. doi:10.1177/1947601910388030

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Yu H, Li X, Sun S, Gao X, Zhou D (2012) c-Met inhibitor SU11274 enhances the response of the prostate cancer cell line DU145 to ionizing radiation. Biochem Biophys Res Commun 427(3):659–665. doi:10.1016/j.bbrc.2012.09.117

    Article  CAS  PubMed  Google Scholar 

  102. Li B, Torossian A, Sun Y, Du R, Dicker AP, Lu B (2012) Higher levels of c-Met expression and phosphorylation identify cell lines with increased sensitivity to AMG-458, a novel selective c-Met inhibitor with radiosensitizing effects. Int J Radiat Oncol Biol Phys 84(4):e525–e531. doi:10.1016/j.ijrobp.2012.06.025

    Article  CAS  PubMed  Google Scholar 

  103. Lin CI, Whang EE, Donner DB, Du J, Lorch J, He F, Jiang X, Price BD, Moore FD Jr, Ruan DT (2010) Autophagy induction with RAD001 enhances chemosensitivity and radiosensitivity through Met inhibition in papillary thyroid cancer. Mol Can Res 8(9):1217–1226. doi:10.1158/1541-7786.MCR-10-0162

    Article  CAS  Google Scholar 

  104. Buchanan IM, Scott T, Tandle AT, Burgan WE, Burgess TL, Tofilon PJ, Camphausen K (2011) Radiosensitization of glioma cells by modulation of Met signalling with the hepatocyte growth factor neutralizing antibody, AMG102. J Cell Mol Med 15(9):1999–2006. doi:10.1111/j.1582-4934.2010.01122.x

    Article  CAS  PubMed  Google Scholar 

  105. Lal B, Xia S, Abounader R, Laterra J (2005) Targeting the c-Met pathway potentiates glioblastoma responses to gamma-radiation. Clin Cancer Res 11(12):4479–4486. doi:10.1158/1078-0432.CCR-05-0166

    Article  CAS  PubMed  Google Scholar 

  106. Peters S, Adjei AA (2012) MET: a promising anticancer therapeutic target. Nat Rev Clin Oncol 9(6):314–326. doi:10.1038/nrclinonc.2012.71

    Article  CAS  PubMed  Google Scholar 

  107. Liu JP, Baker J, Perkins AS, Robertson EJ, Efstratiadis A (1993) Mice carrying null mutations of the genes encoding insulin-like growth factor I (Igf-1) and type 1 IGF receptor (Igf1r). Cell 75(1):59–72

    CAS  PubMed  Google Scholar 

  108. Jacobs CI (2008) A review of the role of insulin-like growth factor 2 in malignancy and its potential as a modifier of radiation sensitivity. Clin Oncol (R Coll Radiol) 20(5):345–352. doi:10.1016/j.clon.2008.02.004

    Article  CAS  Google Scholar 

  109. Samani AA, Yakar S, LeRoith D, Brodt P (2007) The role of the IGF system in cancer growth and metastasis: overview and recent insights. Endocr Rev 28(1):20–47. doi:10.1210/er.2006-0001

    Article  CAS  PubMed  Google Scholar 

  110. Turner BC, Haffty BG, Narayanan L, Yuan J, Havre PA, Gumbs AA, Kaplan L, Burgaud JL, Carter D, Baserga R, Glazer PM (1997) Insulin-like growth factor-I receptor overexpression mediates cellular radioresistance and local breast cancer recurrence after lumpectomy and radiation. Cancer Res 57(15):3079–3083

    CAS  PubMed  Google Scholar 

  111. 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. Int J Radiat Oncol Biol Phys 79(4):1179–1187. doi:10.1016/j.ijrobp.2010.10.003

    Article  CAS  PubMed  Google Scholar 

  112. Allen GW, Saba C, Armstrong EA, Huang SM, Benavente S, Ludwig DL, Hicklin DJ, Harari PM (2007) Insulin-like growth factor-I receptor signaling blockade combined with radiation. Cancer Res 67(3):1155–1162. doi:10.1158/0008-5472.CAN-06-2000

    Article  CAS  PubMed  Google Scholar 

  113. 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(45):5262–5273. doi:10.1038/onc.2013.460

    Article  CAS  PubMed  Google Scholar 

  114. Jin Q, Esteva FJ (2008) Cross-talk between the ErbB/HER family and the type I insulin-like growth factor receptor signaling pathway in breast cancer. J Mammary Gland Biol Neoplasia 13(4):485–498. doi:10.1007/s10911-008-9107-3

    Article  PubMed  Google Scholar 

  115. Jones HE, Dutkowski CM, Barrow D, Harper ME, Wakeling AE, Nicholson RI (1997) New EGF-R selective tyrosine kinase inhibitor reveals variable growth responses in prostate carcinoma cell lines PC-3 and DU-145. Int J Cancer 71(6):1010–1018

    Article  CAS  PubMed  Google Scholar 

  116. Li P, Veldwijk MR, Zhang Q, Li ZB, Xu WC, Fu S (2013) Co-inhibition of epidermal growth factor receptor and insulin-like growth factor receptor 1 enhances radiosensitivity in human breast cancer cells. BMC Cancer 13:297. doi:10.1186/1471-2407-13-297

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL (1987) Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 235(4785):177–182

    Article  CAS  PubMed  Google Scholar 

  118. Janjigian YY, Werner D, Pauligk C, Steinmetz K, Kelsen DP, Jager E, Altmannsberger HM, Robinson E, Tafe LJ, Tang LH, Shah MA, Al-Batran SE (2012) Prognosis of metastatic gastric and gastroesophageal junction cancer by HER2 status: a European and USA International collaborative analysis. Ann Oncol 23(10):2656–2662. doi:10.1093/annonc/mds104

    Article  CAS  PubMed  Google Scholar 

  119. Hong TS, Wo JY, Kwak EL (2013) Targeted therapies with chemoradiation in esophageal cancer: development and future directions. Semin Radiat Oncol 23(1):31–37. doi:10.1016/j.semradonc.2012.09.004

    Article  PubMed  Google Scholar 

  120. Pietras RJ, Poen JC, Gallardo D, Wongvipat PN, Lee HJ, Slamon DJ (1999) Monoclonal antibody to HER-2/neuroreceptor modulates repair of radiation-induced DNA damage and enhances radiosensitivity of human breast cancer cells overexpressing this oncogene. Cancer Res 59(6):1347–1355

    CAS  PubMed  Google Scholar 

  121. Sambade MJ, Camp JT, Kimple RJ, Sartor CI, Shields JM (2009) Mechanism of lapatinib-mediated radiosensitization of breast cancer cells is primarily by inhibition of the Raf>MEK>ERK mitogen-activated protein kinase cascade and radiosensitization of lapatinib-resistant cells restored by direct inhibition of MEK. Radiother Oncol 93(3):639–644. doi:10.1016/j.radonc.2009.09.006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Kimple RJ, Vaseva AV, Cox AD, Baerman KM, Calvo BF, Tepper JE, Shields JM, Sartor CI (2010) Radiosensitization of epidermal growth factor receptor/HER2-positive pancreatic cancer is mediated by inhibition of Akt independent of ras mutational status. Clin Cancer Res 16(3):912–923. doi:10.1158/1078-0432.CCR-09-1324

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Sambade MJ, Kimple RJ, Camp JT, Peters E, Livasy CA, Sartor CI, Shields JM (2010) Lapatinib in combination with radiation diminishes tumor regrowth in HER2+ and basal-like/EGFR+ breast tumor xenografts. Int J Radiat Oncol Biol Phys 77(2):575–581. doi:10.1016/j.ijrobp.2009.12.063

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Safran H, Dipetrillo T, Akerman P, Ng T, Evans D, Steinhoff M, Benton D, Purviance J, Goldstein L, Tantravahi U, Kennedy T (2007) Phase I/II study of trastuzumab, paclitaxel, cisplatin and radiation for locally advanced, HER2 overexpressing, esophageal adenocarcinoma. Int J Radiat Oncol Biol Phys 67(2):405–409. doi:10.1016/j.ijrobp.2006.08.076

    Article  CAS  PubMed  Google Scholar 

  125. Perez EA, Romond EH, Suman VJ, Jeong JH, Davidson NE, Geyer CE Jr, Martino S, Mamounas EP, Kaufman PA, Wolmark N (2011) Four-year follow-up of trastuzumab plus adjuvant chemotherapy for operable human epidermal growth factor receptor 2-positive breast cancer: joint analysis of data from NCCTG N9831 and NSABP B-31. J Clin Oncol 29(25):3366–3373. doi:10.1200/JCO.2011.35.0868

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Turner N, Grose R (2010) Fibroblast growth factor signalling: from development to cancer. Nat Rev Cancer 10(2):116–129. doi:10.1038/nrc2780

    Article  CAS  PubMed  Google Scholar 

  127. Eswarakumar VP, Lax I, Schlessinger J (2005) Cellular signaling by fibroblast growth factor receptors. Cytokine Growth Factor Rev 16(2):139–149. doi:10.1016/j.cytogfr.2005.01.001

    Article  CAS  PubMed  Google Scholar 

  128. Cappellen D, De Oliveira C, Ricol D, de Medina S, Bourdin J, Sastre-Garau X, Chopin D, Thiery JP, Radvanyi F (1999) Frequent activating mutations of FGFR3 in human bladder and cervix carcinomas. Nat Genet 23(1):18–20. doi:10.1038/12615

    Article  CAS  PubMed  Google Scholar 

  129. Dutt A, Salvesen HB, Chen TH, Ramos AH, Onofrio RC, Hatton C, Nicoletti R, Winckler W, Grewal R, Hanna M, Wyhs N, Ziaugra L, Richter DJ, Trovik J, Engelsen IB, Stefansson IM, Fennell T, Cibulskis K, Zody MC, Akslen LA, Gabriel S, Wong KK, Sellers WR, Meyerson M, Greulich H (2008) Drug-sensitive FGFR2 mutations in endometrial carcinoma. Proc Natl Acad Sci U S A 105(25):8713–8717. doi:10.1073/pnas.0803379105

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Weiss J, Sos ML, Seidel D, Peifer M, Zander T, Heuckmann JM, Ullrich RT, Menon R, Maier S, Soltermann A, Moch H, Wagener P, Fischer F, Heynck S, Koker M, Schottle J, Leenders F, Gabler F, Dabow I, Querings S, Heukamp LC, Balke-Want H, Ansen S, Rauh D, Baessmann I, Altmuller J, Wainer Z, Conron M, Wright G, Russell P, Solomon B, Brambilla E, Brambilla C, Lorimier P, Sollberg S, Brustugun OT, Engel-Riedel W, Ludwig C, Petersen I, Sanger J, Clement J, Groen H, Timens W, Sietsma H, Thunnissen E, Smit E, Heideman D, Cappuzzo F, Ligorio C, Damiani S, Hallek M, Beroukhim R, Pao W, Klebl B, Baumann M, Buettner R, Ernestus K, Stoelben E, Wolf J, Nurnberg P, Perner S, Thomas RK (2010) Frequent and focal FGFR1 amplification associates with therapeutically tractable FGFR1 dependency in squamous cell lung cancer. Sci Transl Med 2(62):62ra93. doi:10.1126/scitranslmed.3001451

  131. Colvin JS, Bohne BA, Harding GW, McEwen DG, Ornitz DM (1996) Skeletal overgrowth and deafness in mice lacking fibroblast growth factor receptor 3. Nat Genet 12(4):390–397. doi:10.1038/ng0496-390

    Article  CAS  PubMed  Google Scholar 

  132. Brooks AN, Kilgour E, Smith PD (2012) Molecular pathways: fibroblast growth factor signaling: a new therapeutic opportunity in cancer. Clin Cancer Res 18(7):1855–1862. doi:10.1158/1078-0432.CCR-11-0699

    Article  CAS  PubMed  Google Scholar 

  133. Cazet A, Charest J, Bennett DC, Sambrooks CL, Contessa JN (2014) Mannose phosphate isomerase regulates fibroblast growth factor receptor family signaling and glioma radiosensitivity. PLoS One 9(10), e110345. doi:10.1371/journal.pone.0110345

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  134. Fuks Z, Persaud RS, Alfieri A, McLoughlin M, Ehleiter D, Schwartz JL, Seddon AP, Cordon-Cardo C, Haimovitz-Friedman A (1994) Basic fibroblast growth factor protects endothelial cells against radiation-induced programmed cell death in vitro and in vivo. Cancer Res 54(10):2582–2590

    CAS  PubMed  Google Scholar 

  135. Gu Q, Wang D, Wang X, Peng R, Liu J, Jiang T, Wang Z, Wang S, Deng H (2004) Basic fibroblast growth factor inhibits radiation-induced apoptosis of HUVECs. I. The PI3K/AKT pathway and induction of phosphorylation of BAD. Radiat Res 161(6):692–702

    Article  CAS  PubMed  Google Scholar 

  136. Ader I, Toulas C, Dalenc F, Delmas C, Bonnet J, Cohen-Jonathan E, Favre G (2002) RhoB controls the 24 kDa FGF-2-induced radioresistance in HeLa cells by preventing post-mitotic cell death. Oncogene 21(39):5998–6006. doi:10.1038/sj.onc.1205746

    Article  CAS  PubMed  Google Scholar 

  137. Ader I, Delmas C, Skuli N, Bonnet J, Schaeffer P, Bono F, Cohen-Jonathan-Moyal E, Toulas C (2014) Preclinical evidence that SSR128129E--a novel small-molecule multi-fibroblast growth factor receptor blocker--radiosensitises human glioblastoma. Eur J Cancer 50(13):2351–2359. doi:10.1016/j.ejca.2014.05.012

    Article  CAS  PubMed  Google Scholar 

  138. Hsu HW, Wall NR, Hsueh CT, Kim S, Ferris RL, Chen CS, Mirshahidi S (2014) Combination antiangiogenic therapy and radiation in head and neck cancers. Oral Oncol 50(1):19–26. doi:10.1016/j.oraloncology.2013.10.003

    Article  CAS  PubMed  Google Scholar 

  139. Lopez-Chavez A, Carter CA, Giaccone G (2009) The role of KRAS mutations in resistance to EGFR inhibition in the treatment of cancer. Curr Opin Investig Drugs 10(12):1305–1314

    CAS  PubMed  Google Scholar 

  140. Bennett DC, Charest J, Sebolt K, Lehrman M, Rehemtulla A, Contessa JN (2013) High-throughput screening identifies aclacinomycin as a radiosensitizer of EGFR-mutant non-small cell lung cancer. Transl Oncol 6(3):382–391

    Article  PubMed  PubMed Central  Google Scholar 

  141. Mellinghoff IK, Wang MY, Vivanco I, Haas-Kogan DA, Zhu S, Dia EQ, Lu KV, Yoshimoto K, Huang JH, Chute DJ, Riggs BL, Horvath S, Liau LM, Cavenee WK, Rao PN, Beroukhim R, Peck TC, Lee JC, Sellers WR, Stokoe D, Prados M, Cloughesy TF, Sawyers CL, Mischel PS (2005) Molecular determinants of the response of glioblastomas to EGFR kinase inhibitors. N Engl J Med 353(19):2012–2024. doi:10.1056/NEJMoa051918

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Therapeutic Radiology, Yale University School of Medicine, 208040, New Haven, CT, USA

    Thomas J. Hayman & Joseph N. Contessa

Authors
  1. Thomas J. Hayman
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Joseph N. Contessa
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Joseph N. Contessa .

Editor information

Editors and Affiliations

  1. Radiation Oncology Branch, National Cancer Institute, Bethesda, Maryland, USA

    Philip J. Tofilon

  2. 1Radiation Oncology Branch, National Cancer Institute, Bethesda, Maryland, USA

    Kevin Camphausen

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Hayman, T.J., Contessa, J.N. (2017). Receptor Tyrosine Kinases as Targets for Enhancing Tumor Radiosensitivity. In: Tofilon, P., Camphausen, K. (eds) Increasing the Therapeutic Ratio of Radiotherapy. Cancer Drug Discovery and Development. Humana Press, Cham. https://doi.org/10.1007/978-3-319-40854-5_2

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-40854-5_2

  • Published:

  • Publisher Name: Humana Press, Cham

  • Print ISBN: 978-3-319-40852-1

  • Online ISBN: 978-3-319-40854-5

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation