Translational Research



  • Develop a database for biosample collection (virtual tumour bank) and biosample tracking
  • Organise prospective and retrospective collection, deposition and delivery of biomaterials
  • Provide Central Histopathological Review (CHR) to ensure the inclusion of solely Type II tumours into Phase II and to ensure tissue sample quality for experimental work

Description of Work


An outstanding biobank was established by the clinical partners from patients included in the randomised Phase II trial. Collected biomaterials include archival formalin-fixed, paraffin-embedded (FFPE) tumour tissues, biopsies of the actual relapse (fresh-frozen or FFPE), blood fractions (plasma, serum, cell pallets) collected taken at different time-points prior and during study treatment, circulating tumour cells (CTCs) in the blood, as well as ascites and pleural effusion samples.

Archival FFPE tumour tissues

Plasma, serum, cell pellets

Circulating tumour cells (CTCs)

Biopsies of the actual relapse

Ascites and pleura effusions

Companion Diagnostics


  • Determine the exact p53 status in Phase II patients
  • Perform molecular efficacy testing: (1) a functional molecular test (proximity ligation assay) will be developed and evaluated for its value to predict responsiveness to Ganetespib. (2) CTC analysis before and during experimental therapy will be performed and evaluated for its value to monitor responsiveness to Ganetespib.


Functional molecular test (proximity ligation assay) developed

The proximity ligation assay (PLA) is an in situ technology, which allows a sensitive detection of protein, protein interactions. The signal can be localized with single molecule resolution. Specific antibodies recognize the two targets and are subsequently bound by PLA probes. They have a short DNA strand attached, and when in close proximity, they interact, are ligated and amplified via rolling circle amplification. Fluorochrome-labelled probes are then added to visualize the product, which is than seen as bright spot in the fluorescence microscope.

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p53 mutational status in all Phase II patients determined

The GANNET53 project is based on the hypothesis that mutant p53 is stabilized through the chaperon HSP90 and can therefore neither fulfil its function, nor be degraded. This stabilization is a prerequisite for gain-of-function capabilities promoting tumour growth. Furthermore, tumours carrying a missense TP53 mutation develop a dependency on the high protein levels and withdrawal should results in cytotoxicity. The HSP90 inhibitor Ganetespib is used to release stabilized p53 and target it for degradation. The GANNET53 trial includes patients with Type II ovarian cancer. This type of cancer is characterized by an almost ubiquitous presence of TP53 mutations. As part of the companion diagnostics, the TP53 mutation status of all patients is determined. For this purpose, it was mandatory that archival tissue of each patient included in the study was available. This analysis allows linking effects of the treatment to the presence of a TP53 mutation in general, and to certain mutations in specific. Furthermore, those results are the basis for additional projects which are conducted as part of the companion diagnostics, as for example the analysis of circulating DNA.

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Mouse Models and Human Xenografts


  • Provide the most stringent in vivo genetic and pharmacologic proof-of-principle for the underlying treatment concept in engineered mutp53 knock-in mice.
  • Stringently test the Ganetespib-mediated preferential killing of mutp53 cancer cells in human ovarian cancer models (cultured cells and nude mice).


Publication: CELL DEATH AND DIFFERENTIATION (2016), 1–17: Strong antitumor synergy between DNA crosslinking and HSP90 inhibition causes massive premitoticDNA fragmentation in ovarian cancer cells. Kramer D, Stark N, Schulz-Heddergott R, Erytch N, Edmunds S, Roßmann L, Bastians H, Concin N, Moll UM, Dobbelstein M. doi: 10.1038/cdd.2016.124. [Epub ahead of print] PMID: 27834954; Link:;