Molecular Biology of Systemic Radiotherapy

DKFZ Bayer Junior Research Group Molecular Biology of Systemic Radiotherapy

Dr. Martina Benesova

The main goal of E270 is to improve Targeted Alpha Therapies (TAT). To achieve this goal, three main areas closely related to alpha-particle emitting radionuclides - radiobiology, drug design and immunology – are investigated.
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With rapid population growth and aging, cancer is expected to rank as the leading cause of death in every country of the world in the 21st century. The development of improved diagnostic and therapeutic strategies for the management of cancer is, therefore, of utmost importance. Targeted Radionuclide Therapy (TRNT) or “endoradiotherapy” is an attractive treatment option, where radionuclides are directed to particular cancer-associated targets (receptors, antigens, enzymes or other molecular structures) by specific binders. While external beam radiation (conventional radiotherapy) is highly effective in treating local tumors, TRNT has emerged as an effective therapeutic strategy for disseminated (metastasized) disease. Currently, Targeted Alpha Therapy (TAT) represents the most rapidly developing field in nuclear medicine. Alpha particles have high Linear Energy Transfer (LET; 50–230 keV/µm) significantly enhancing relative biological effectiveness of TAT as compared to other commonly used radionuclide therapies. In addition, short penetration depth of 50–100 µm (6 cell diameters) limits damage to the surrounding healthy tissue. Moreover, based on the critical role of the immune system in cancer development and dissemination, TAT may potentially be combined with various strategies triggering immune response in order to achieve enhanced anti-tumor effect and prolonged remission in cancer patients.

The Junior research group Molecular Biology of Systemic Radiotherapy was jointly established by DKFZ and Bayer within their strategic alliance and will pursue highly innovative projects at the frontiers of interdisciplinary cancer research. Our group focuses in particular on alpha particle-emitting radionuclides (e.g., Th-227, Ac-225 and Ra-223), their coordination properties, their physicochemical effects and the respective radiation-induced immune responses and the underlying molecular pathways in the tumor tissue and its microenvironment. In other words, we investigate the mechanisms of effectiveness and resistance towards TAT, with the aim to identify novel cancer targets and therapeutic radiopharmaceuticals. Moreover, we also focus on other prospective therapies which might be beneficially combined with TAT in the future. Successful pre-clinical outcome of above described projects is seen as a powerful basis for the transition towards a contemporary personalized and precision medicine.

Contact

Dr. Martina Benesova
Molecular Biology of Systemic Radiotherapy (E270)
Deutsches Krebsforschungszentrum
Im Neuenheimer Feld 223
69120 Heidelberg
Tel: +49 6221 42 5355

Selected Publications

  • Schniering J, Benešová M, Brunner M, Haller S, Cohrs S, Frauenfelder T, Vrugt B, Feghali-Bostwick C, Schibli R, Distler O, Müller C, Maurer B. Visualisation of interstitial lung disease by molecular imaging of integrin αvβ3 and somatostatin receptor 2. Ann Rheum Dis 2019; 78(2): 218–227.
  • Benešová M, Umbricht CA, Schibli R, Müller C. Albumin-Binding PSMA Ligands: Optimization of the Tissue Distribution Profile. Mol Pharmaceutics 2018; 15(3): 934–994.
  • Benešová M, Bauder-Wüst U, Schäfer M, Klika KD, Mier W, Haberkorn U, Kopka K, Eder M. New linker modifications influence the PSMA targeting and pharmacokinetic properties of DOTA-conjugated PSMA inhibitors. J Med Chem 2016; 59(5): 1761–1775.
  • Benešová M, Schäfer M, Bauder-Wüst U, Afshar-Oromieh A, Kratochwil C, Mier W, Haberkorn U, Kopka K, Eder M. Preclinical evaluation of a tailor-made DOTA-conjugated PSMA inhibitor with optimized linker moiety for imaging and endoradiotherapy of prostate cancer. JNM 2015; 56(6): 914–920.
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