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PACT Pharmaceuticals – signalling pathways and RNA interference

In March 2010, PACT Pharmaceuticals, the founding concept of Professor Dr. Michael Boutros’ team at the German Cancer Research Centre, was selected as one of ten outstanding business concepts in the Science4Life business plan competition intermediary award. Around 200 business plans were originally submitted. PACT develops innovative cancer therapeutics that target the signalling pathways involved in tumour pathogenesis.

Prof. Dr. Michael Boutros © ZBIO

PACT Pharmaceuticals is to be spun out from the "Signalling and Functional Genomics" department of the German Cancer Research Centre (DKFZ) in Heidelberg. The start-up develops innovative pharmaceutically active substances for the more efficient and less invasive therapy of cancer. These drugs target signalling networks that are active during tumour development and in tumour stem cells. The use of an innovative technology platform based on the combination of RNAi and drug screening led to the identification and medical and chemical optimisation of therapeutics with a limited number of side effects.

The founding team includes Prof. Dr. Michael Boutros, whose concept was successful in the BMBF's first Go-Bio competition back in 2006, and his colleagues Dr. Sandra Steinbrink and Dr. Friedrich Georg Hansske.

Sandra Steinbrink was involved in the development of the core technologies of PACT in the department of Prof. Boutros and is now transferring her knowledge to PACT Pharmaceuticals where she is project manager. Hansske has gained in-depth experience in industry, both at Boehringer Mannheim as well as in his role as founder and CEO of BioLeads GmbH and a number of other companies.

An interdisciplinary team of chemists, engineers and technicians is focusing on the identification and development of the substances. The products will initially be preclinically validated substances that will subsequently be licensed to other companies or be developed further in cooperation with industrial partners.

Signalling pathways and functional genomics

Prof. Boutros is head of the “Signalling and Functional Genomics” department at the DKFZ and is also chair of the Department of Cell and Molecular Biology at the Mannheim Medical Faculty of the University of Heidelberg (ZBIO). The chair, which was established in 2008, is a cooperation unit with the DKFZ and is located at the interdisciplinary Centre of Biomedicine and Medical Technology Mannheim (CBTM).

Systematic RNA interference © Boutros, DKFZ

The business concept of PACT Pharmaceuticals is based on scientific research carried out by Prof. Boutros and his team, involving cellular signalling and its role in the development and differentiation of organisms as well as the role of faulty signalling in the development of diseases. The researchers develop and use high-throughput screening methods (genomic, cell biological and genetic ones) to screen the human genome and the genome of model organisms for new functions. A major focus concentrates on automated RNA interference methods (RNAi screens) that enable the silencing of genes and deduce their normal and disease-specific functions. The researchers' goal is to identify new targets for cancer-related processes.

An example of the research in the Signalling and Functional Genomics department is the EU-funded cooperative project CancerPathways (www.cancerpathways.eu), which is being carried out in cooperation with 7 European partners. The CancerPathways consortium's goal is to identify new targets and drugs for therapeutic applications.

One example: Wnt signalling

The transfer of cellular signals is of key importance in many processes, for example the regulation of stem cells, defects of the innate immune system and the development of cancer.

The development of human tumours is often trigged by mutations of signalling factors. Human colorectal cancer is associated with mutations of the APC gene that is of huge importance for the regulation of Wnt signalling. The protein encoded by APC (Adenomatous polyposis coli), a tumour suppressor gene, plays a key role in the degradation of beta catenin. Mutations that lead to the inactivation of the APC tumour suppressor or activation of beta catenin are found in around 90 per cent of all colorectal cancers. However, Wnt-activating mutations are also known for many other types of cancers, including liver cancer.

Michael Boutros’ team focuses on the regulation of Wnt signalling in developmental processes and in the development of diseases. The researchers focus predominantly on the identification of new components and the investigation of specific processes involving Wnt ligands. The use of new high-throughput RNAi screening methods enable the screening of human cancer cell lines and the identification of new targets and drugs. The work revolving around Wnt signalling and other signalling pathways form the scientific basis of PACT.

Further information:
Prof. Dr. Michael Boutros or Dr. Sandra Steinbrink
German Cancer Research Centre
Im Neuenheimer Feld 580
69120 Heidelberg
Tel.: +49 (0)6221-42 1951
Fax: +49 (0)6221-42 1959
E-mail: m.boutros(at)dkfz.de
Website address: https://www.gesundheitsindustrie-bw.de/en/article/news/pact-pharmaceuticals-signalling-pathways-and-rna-interference