TP5 Biologically individualized ion therapy of lung carcinoma
Molecular targets with very high level of evidence in regard to predictive value and usability for therapy exist for patients with non-small cell lung carcinoma (NSCLC). This applies for NSCLC tumors with activating mutations of epidermal growth factor receptor (EGFR) which typically show a high sensitivity to inhibitors of EGFR signaling (RKTi, Gefitinib, or Erlotinib).
NSCLC patients with EGFR amplification show a higher therapy response when treated with therapeutic EGFR antibodies Cetuximab or Panitumumab). In addition, patients who’s tumors show an adenocarcinoma histology benefit from anti-angiogenesis therapy (Bevacizumab, anti-VEGF) in combination with chemotherapy. Altogether, 20-40% of lung cancer patients will benefit from biologically individualized therapy after assessing their molecular predictors.
Considering the high incidence of bronchial carcinoma (most frequent malign disease in industrial nations) this is of high clinical relevance and in our department more than 600 patients per year have the chance to benefit from molecular diagnostics in combination with radiotherapy.
Within this project we study the sensitivity of these molecular markers to ion irradiation in a molecular distinct collective of patients in combination with their respective molecular therapy (especially inhibitors of EGFR, ALK, and VEGF signaling) with the aim to biologically optimize ion therapy on the local and the systemic level.
Dai Y, Wei Q, Schwager C, Moustafa M, Zhou C, Lipson KE, Weichert W, Debus J, Abdollahi A. Synergistic effects of crizotinib and radiotherapy in experimental EML4-ALK fusion positive lung cancer. Radiother Oncol. 2015 Feb;114(2):173-81
Niklas M, Abdollahi A, Akselrod MS, Debus J, Jäkel O, Greilich S. Subcellular spatial correlation of particle traversal and biological response in clinical ion beams. Int J Radiat Oncol Biol Phys. 2013 Dec 1;87(5):1141-7
Sharungbam GD, Schwager C, Chiblak S, Brons S, Hlatky L, Haberer T, Debus J, Abdollahi A. Identification of stable endogenous control genes for transcriptional profiling of photon, proton and carbon-ion irradiated cells. Radiat Oncol. 2012 May 17;7:70
Timke C, Zieher H, Roth A, Hauser K, Lipson KE, Weber KJ, Debus J, Abdollahi A, Huber PE. Combination of vascular endothelial growth factor receptor/platelet-derived growth factor receptor inhibition markedly improves radiation tumor therapy. Clin Cancer Res. 2008 Apr 1;14(7):2210-9