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Strahlentherapie und Onkologie

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01-11-2012 | Originalien

Molekulare Signalwege

Mechanismen und klinische Anwendung

Authors: Prof. Dr. N. Cordes, Prof. Dr. F. Rödel, Prof. Dr. H.-P. Rodemann

Published in: Strahlentherapie und Onkologie | Special Issue 3/2012

Zusammenfassung

Dieser kurze Abriss zur Rolle der experimentellen Radioonkologie stellt einige herausragende neue Forschungsthemen und Forschungsansätze heraus, welche großes Potenzial für die Optimierung der modernen Radioonkologie bieten. Darüber hinaus sind viele Forschungsfelder wie Hypoxie, Angiogenese, Immunsystem, Metabolismus, u. v. a. m. zu nennen, die einen wesentlichen Anteil an unserem heutigen Kenntnisstand zur Tumor- und Strahlenbiologie besitzen. Welche neuen Einblicke und therapeutischen Möglichkeiten durch Initiativen wie das „Human Cancer Genome Project“ oder neue Verfahren wie das „next-generation sequencing„ eröffnet werden, können wir momentan schwer vorhersehen. Eines wissen wir jedoch mit Sicherheit: Die Strahlenbiologie hat und wird in zunehmendem Maße zu einer Verbesserung der Radioonkologie beigetragen.

Cordes N, Beinke C, Plasswilm L et al (2004) Irradiation and various cytotoxic drugs enhance tyrosine phosphorylation and beta(1)-integrin clustering in human A549 lung cancer cells in a substratum-dependent manner in vitro. Strahlenther Onkol 180(3):157–164PubMedCrossRef

Cordes N, Meineke V (2003) Cell adhesion-mediated radioresistance (CAM-RR). Extracellular matrix-dependent improvement of cell survival in human tumor and normal cells in vitro. Strahlenther Onkol 179(5):337–344PubMedCrossRef

Hehlgans S, Haase M, Cordes N (2007) Signalling via integrins: implications for cell survival and anticancer strategies. Biochim Biophys Acta 1775(1):163–180PubMed

Eke I, Deuse Y, Hehlgans S et al (2012) Beta1 Integrin/FAK/cortactin signaling is essential for human head and neck cancer resistance to radiotherapy. J Clin Invest 122(4):1529–1540PubMedCrossRef

Hehlgans S, Eke I, Cordes N (2012) Targeting FAK radiosensitizes 3-dimensional grown human HNSCC cells through reduced Akt1 and MEK1/2 signaling. Int J Radiat Oncol Biol Phys 83(5):669–676CrossRef

Eke I, Cordes N (2011) Radiobiology goes 3D: how ECM and cell morphology impact on cell survival after irradiation. Radiother Oncol 99(3):271–278PubMedCrossRef

Storch K, Eke I, Borgmann K et al (2010) Three-dimensional cell growth confers radioresistance by chromatin density modification. Cancer Res 70(10):3925–3934PubMedCrossRef

Eke I, Koch U, Hehlgans S et al (2010) PINCH1 regulates Akt1 activation and enhances radioresistance by inhibiting PP1alpha. J Clin Invest 120(7):2516–2527PubMedCrossRef

Eke I, Cordes N (2011) Dual targeting of EGFR and focal adhesion kinase in 3D grown HNSCC cell cultures. Radiother Oncol 99(3):279–286PubMedCrossRef

10.

Nyati MK, Morgan MA, Feng FY et al (2006) Integration of EGFR inhibitors with radiochemotherapy. Nat Rev Cancer 6(11):876–885PubMedCrossRef

11.

Rodemann HP, Dittmann K, Toulany M (2007) Radiation-induced EGFR-signaling and control of DNA-damage repair. Int J Radiat Biol 83(11–12):781–791

12.

Toulany M, Baumann M, Rodemann HP (2007) Stimulated PI3K-AKT signaling mediated through ligand or radiation-induced EGFR depends indirectly, but not directly, on constitutive K-Ras activity. Mol Cancer Res 5(8):863–872PubMedCrossRef

13.

Golding SE, Morgan RN, Adams BR et al (2009) Pro-survival AKT and ERK signaling from EGFR and mutant EGFRvIII enhances DNA double-strand break repair in human glioma cells. Cancer Biol Ther 8(8):730–738PubMedCrossRef

14.

Kriegs M, Kasten-Pisula U, Rieckmann T et al (2010) The epidermal growth factor receptor modulates DNA double-strand break repair by regulating non-homologous end-joining. DNA Repair (Amst) 9(8):889–897

15.

Gupta AK, McKenna WG, Weber CN et al (2002) Local recurrence in head and neck cancer: relationship to radiation resistance and signal transduction. Clin Cancer Res 8(3):885–892PubMed

16.

Toulany M, Rodemann HP (2010) Membrane receptor signaling and control of DNA repair after exposure to ionizing radiation. Nuklearmedizin 49(Suppl 1):S 26–30

17.

Dittmann K, Mayer C, Fehrenbacher B et al (2005) Radiation-induced epidermal growth factor receptor nuclear import is linked to activation of DNA-dependent protein kinase. J Biol Chem 280(35):31182–31189PubMedCrossRef

18.

Liccardi G, Hartley JA, Hochhauser D (2011) EGFR nuclear translocation modulates DNA repair following cisplatin and ionizing radiation treatment. Cancer Res 71(3):1103–1114PubMedCrossRef

19.

Dittmann K, Mayer C, Fehrenbacher B et al (2011) Nuclear epidermal growth factor receptor modulates cellular radio-sensitivity by regulation of chromatin access. Radiother Oncol 99(3):317–322PubMedCrossRef

20.

Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144(5):646–674PubMedCrossRef

21.

Altieri DC (2008) Survivin, cancer networks and pathway-directed drug discovery. Nat Rev Cancer 8(1):61–70PubMedCrossRef

22.

Capalbo G, Rodel C, Stauber RH et al (2007) The role of survivin for radiation therapy. Prognostic and predictive factor and therapeutic target. Strahlenther Onkol 183(11):593–599PubMedCrossRef

23.

Rodel F, Reichert S, Sprenger T et al (2011) The role of survivin for radiation oncology: moving beyond apoptosis inhibition. Curr Med Chem 18(2):191–199PubMedCrossRef

24.

Rodel F, Hoffmann J, Grabenbauer GG et al (2002) High survivin expression is associated with reduced apoptosis in rectal cancer and may predict disease-free survival after preoperative radiochemotherapy and surgical resection. Strahlenther Onkol 178(8):426–435PubMedCrossRef

25.

Sprenger T, Rodel F, Beissbarth T et al (2011) Failure of downregulation of survivin following neoadjuvant radiochemotherapy in rectal cancer is associated with distant metastases and shortened survival. Clin Cancer Res 17(6):1623–1631PubMedCrossRef

26.

Mehrotra S, Languino LR, Raskett CM et al (2010) IAP regulation of metastasis. Cancer Cell 17(1):53–64PubMedCrossRef

27.

Rodel C, Haas J, Groth A et al (2003) Spontaneous and radiation-induced apoptosis in colorectal carcinoma cells with different intrinsic radiosensitivities: survivin as a radioresistance factor. Int J Radiat Oncol Biol Phys 55(5):1341–1347PubMedCrossRef

28.

Rodel F, Hoffmann J, Distel L et al (2005) Survivin as a radioresistance factor, and prognostic and therapeutic target for radiotherapy in rectal cancer. Cancer Res 65(11):4881–4887PubMedCrossRef

29.

Rodel F, Frey B, Leitmann W et al (2008) Survivin antisense oligonucleotides effectively radiosensitize colorectal cancer cells in both tissue culture and murine xenograft models. Int J Radiat Oncol Biol Phys 71(1):247–255PubMedCrossRef

30.

Capalbo G, Dittmann K, Weiss C et al (2010) Radiation-induced survivin nuclear accumulation is linked to DNA damage repair. Int J Radiat Oncol Biol Phys 77(1):226–234PubMedCrossRef

Title: Molekulare Signalwege
Mechanismen und klinische Anwendung
Authors: Prof. Dr. N. Cordes
Prof. Dr. F. Rödel
Prof. Dr. H.-P. Rodemann
Publication date: 01-11-2012
Publisher: Springer-Verlag
Published in: Strahlentherapie und Onkologie / Issue Special Issue 3/2012
Print ISSN: 0179-7158
Electronic ISSN: 1439-099X
DOI: https://doi.org/10.1007/s00066-012-0205-1

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Molekulare Signalwege

Mechanismen und klinische Anwendung

Zusammenfassung

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Zusammenfassung

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