gms | German Medical Science

60th Annual Meeting of the German Society for Neuropathology and Neuroanatomy (DGNN)

German Society for Neuropathology and Neuroanatomy

26. - 28.08.2015, Berlin

PDA66 – a small molecule with broad pre-clinical activity against Glioblastoma

Meeting Abstract

  • author presenting/speaker Christian Eisenlöffel - University of Leipzig, Division for Neuropathology, Leipzig, Germany
  • Moritz Frech - University of Rostock, AKos, Rostock, Germany
  • Arndt Rolfs - University of Rostock, AKos, Rostock, Germany
  • Matthias Beller - LIKAT, Rostock, Germany
  • Anahit Pews-Davtyan - LIKAT, Rostock, Germany
  • Ulf Nestler - University of Leipzig, Department for Neurosurgery, Leipzig, Germany
  • Christos Trantakis - SanaKliniken, Clinic for Head- and Spinalmicrosurgery, Borna, Germany
  • Farid Youssef - Helios Kliniken, Department for Neurosurgery, Plauen, Germany
  • Felicitas Merz - University of Leipzig, Institute of Anatomy, Leipzig, Germany
  • corresponding author Wolf Müller - University of Leipzig, Division for Neuropathology, Leipzig, Germany

Deutsche Gesellschaft für Neuropathologie und Neuroanatomie. 60th Annual Meeting of the German Society for Neuropathology and Neuroanatomy (DGNN). Berlin, 26.-28.08.2015. Düsseldorf: German Medical Science GMS Publishing House; 2015. Doc15dgnnP55

doi: 10.3205/15dgnn79, urn:nbn:de:0183-15dgnn794

Published: August 25, 2015

© 2015 Eisenlöffel et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. See license information at



Glioblastomas (GBM) are the most common intrinsic brain tumors. The current standard of care consists of surgical treatment, radiotherapy and adjuvant treatment with the alkylating agent Temozolomide. Despite major scientific efforts and progress these tumors are of dismal prognosis with median overall survival times of 15 months. A major obstacle when applying chemotherapy for tumors of the central nervous system is the blood brain barrier (BBB). It can inhibit high-molecular, hydrophilic substances from reaching the site of the lesion. Furthermore, agents thought to act on singular molecular targets (so called targeted therapies) might display only small effects, especially in tumors with large intratumoral heterogeneity of cellular phenotypes and genotypes as it is the case in Glioblastoma multiforme. In addition, putative tumor initiating cells or 'cancer stem cells' (CSC) –slowly dividing multipotent cells within the tumor - seem to be highly resistant to radio- and chemotherapy and to be the source of tumor recurrences.

Thus the demands for novel therapeutics are (amongst others): passage of the BBB, broad antineoplastic activity against different cellular phenotypes including putative CSC and possible synergisms with current treatment approaches.

PDA66 is a lipophilic small molecule with low molecular weight of 356 Da. It has shown broad activity in cancer cell lines of hematological cancers and carcinomas, the putative underlying mechanism is the inhibition of microtubule-dynamics. From earlier pharmakokinetic studies there is limited evidence, that after intraperitoneal injection PDA66 is distributed to the brain parenchyma in concentrations equal to the plasma levels.

The substance showed antineoplastic activity in several commercial GBM-cell (U87, U251, A-172) with half maximal inhibitory concentrations (IC50) of less than 2µM, up to 150 times less than the currently used agent Temozolomide (IC50 larger than 300µM). While there was no additive effect in concomitant treatment with Temozolomide, we are currently evaluating a possible synergism of PDA66-treatment with low dose radiation. PDA66 induced apoptosis in serum free primary spheroid cultures from human GBM-samples (putative cancer stem cells). Finally, the antiproliferative and pro-apoptotic effects of PDA66 were evaluated in slicecultures of freshly ressected GBM's.

We present a small molecule with promising activity against GBM on several pre-clinical levels. These results warrant further pre-clinical and possibly clinical testing.