Ivana Dokic, PhD

Radiobiology of novel particle beams for hadron therapy

Hadron therapy is a promising technique for cancer treatment and has received increasingly attention over the last decades. This is due to the favorable physical characteristics of charged particle beams that allow highly conformal dose distributions in the tumor region while sparing adjacent normal tissues (organs at risks). Interest for clinical applications of hadron therapy has been rapidly increased due to its beneficial effects for certain tumor patients. Hadron therapy is characterized by high linear energy transfer (LET) irradiation which delivers larger amount of energy per particle track length, which induces complex, difficult to repair DNA damage.  However, biological effectiveness, depth-dose and lateral dose distributions can differ between different particle beams. Based on these differences and tumor characteristics the optimal beam therapy could be individualized for each cell/tumor type. Nevertheless, some tumors, such as glioblastoma and pancreatic cancer, and in particular hypoxic tumors, are extremely radioresistant and difficult to treat.  Molecular mechanisms behind tumor radioresistance are complex and many events still remain unclear. Therefore, the need for understanding the effects of particle radiotherapy (mono-, or combined) on biological processes in tumor and non-transformed cells is of outmost importance for current therapy improvement and future clinical applications.

 

Projects and collaborations:

Our team developed a robust experimental platform which integrates biology, physics, biochemistry. It allows for studying and comparing radiobiological effects of four promising radiation qualities (1H, 4He, 12C, 16O) in vitro (normoxic and hypoxic conditions) and in vivo  at Heidelberg Ion Therapy Center (HIT).

 

  • Pharmacological and genetical alteration of selected target molecules for combined chemo- and radiotherapy (collaboration with Merck KGaA).
  • OMICS approach: Comparative transcriptome, proteome and phosphoproteome profiling for different irradiation modalities aim to understand signaling networks and determine potential molecular targets in extremely resistant tumor cells (collaboration with Dr. M. Schnölzer at DKFZ Proteome Core Facility and Dr. M. Knoll, work group Integrative Omics in Radiation Oncology) .
  •  Investigation of spatio-temporal particle-cell interactions, DNA damage formation and cell fate on microscopic scale, using biophysical hybrid detector (Cell-Fit-HD) technology (collaboration with Dr. M.Niklas, work group Next Generation Biophysical Hybrid Detectors).
  • Implementation of in vitro obtained experimental data in advanced biophysical models (Monte Carlo; MC) for predicting tumor response to radiotherapy and treatment planning (collaboration with Dr. A. Mairani, group Biophysics in Particle Therapy at HUMS/HIT). 

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Selected publications

 

Next generation multi-scale biophysical characterization of high precision cancer particle radiotherapy using clinical proton, helium-, carbon- and oxygen ion beams.

Dokic I, Mairani A, Niklas M, Zimmermann F, Chaudhri N, Krunic D, Tessonnier T, Ferrari A, Parodi K, Jäkel O, Debus J, Haberer T, Abdollahi A. Oncotarget. 2016 Aug 30;7(35):56676-56689. doi: 10.18632/oncotarget.10996.

 

Correlation of Particle Traversals with Clonogenic Survival Using Cell-Fluorescent Ion Track Hybrid Detector.

Dokic I, Niklas M, Zimmermann F, Mairani A, Seidel P, Krunic D, Jäkel O, Debus J, Greilich S, Abdollahi A.

Front Oncol. 2015 Dec 7;5:275. doi: 10.3389/fonc.2015.00275. eCollection 2015.

 

Deciphering the Acute Cellular Phosphoproteome Response to Irradiation with X-rays, Protons and Carbon Ions.

Winter M, Dokic I, Schlegel J, Warnken U, Debus J, Abdollahi A, Schnölzer M. Mol Cell Proteomics. 2017 May;16(5):855-872. doi: 10.1074/mcp.M116.066597. Epub 2017 Mar 16.

 

Overcoming hypoxia-induced tumor radioresistance in non-small cell lung cancer by targeting DNA-dependent protein kinase in combination with carbon ion irradiation.

Klein C, Dokic I, Mairani A, Mein S, Brons S, Häring P, Haberer T, Jäkel O, Zimmermann A, Zenke F, Blaukat A, Debus J, Abdollahi A. Radiat Oncol. 2017 Dec 29;12(1):208. doi: 10.1186/s13014-017-0939-0.

 

Biologically optimized helium ion plans: calculation approach and its in vitro validation.

Mairani A, Dokic I, Magro G, Tessonnier T, Kamp F, Carlson DJ, Ciocca M, Cerutti F, Sala PR, Ferrari A, Böhlen TT, Jäkel O, Parodi K, Debus J, Abdollahi A, Haberer T. Phys Med Biol. 2016 Jun 7;61(11):4283-99. doi: 10.1088/0031-9155/61/11/4283. Epub 2016 May 20.

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